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Infection with Pseudomonas maltophilia hospital outbreak due to contaminated disinfectant.

Between August, 1973, and May, 1974, Pseudomonas maltophilia was isolated from 63 patients in the King Edward Memorial Hospital for Women, Subiaco, Western Australia. Primary cultures were obtained mainly from specimens of urine from adults, and from intraarterial catheter tips and umbilical swabs from neonates. In most cases the organism appeared to be a contaminant, but in seven it was responsible for infection. The source of the organism was deionized water used for diluting Savlon concentrate (chlorhexidine, 1-5%; cetrimide, 15%). In the 17 months since the method of preparation and distribution of Savlon to the wards was altered, Ps. maltophilia has not been isolated from either clinical specimens or hospital disinfectants.

Adult↗

Infections with Pseudomonas paucimobilis: report of four cases and review.

Pseudomonas paucimobilis (formerly CDC group IIK, biotype 1) is a strictly aerobic, nonfermenting, oxidase- and catalase-positive, gram-negative bacillus that is widely distributed in water and soil. Its name derives from the difficulty encountered in demonstrating its motility, even in liquid media. This microorganism is responsible for two types of infection in humans: sporadic or community-acquired infections, probably of endogenous or environmental origin (bacteremia, meningitis, urinary tract infection, and wound infection); and outbreaks of nosocomial infection associated with the contamination of sterile fluids employed in hospitals. We present four cases of infection caused by P. paucimobilis (two of bacteremia, one of leg ulcer infection, and one of cervical adenitis). The majority of infections produced by P. paucimobilis have a good prognosis; no deaths related to this entity have been reported in the literature. The published results of susceptibility tests suggest that the aminoglycosides (either alone or in combination with a beta-lactam antibiotic) or the quinolone may be the agents of choice in the treatment of these infections.

Adult↗

Cystic fibrosis transmembrane conductance regulator (CFTR)-mediated residual chloride secretion does not protect against early chronic Pseudomonas aeruginosa infection in F508del homozygous cystic fibrosis patients.

Cystic fibrosis (CF) disease severity is characterized by a broad variability that has been attributed, in addition to the CF transmembrane conductance regulator (CFTR) genotype, to modulating factors such as CFTR-mediated residual chloride (Cl-) secretion. Moreover, CFTR has been suggested to function as a receptor for Pseudomonas aeruginosa (PA). In this study, we investigated whether or not the presence of residual Cl- secretion protects against early chronic PA colonization of patients' airways. Excluding influences on the phenotype caused by different CFTR mutations, we evaluated a cohort of F508del homozygous individuals with respect to the correlation between residual Cl- secretion and the age of onset of PA colonization as an important marker of clinical phenotype. A group with early chronic PA colonization before the age of 7 y (n = 14) was compared with a cohort that had no initial PA detection at least until the age of 13 y (n = 10). We determined the Cl- transport properties by using the intestinal current measurement in rectal suction biopsies. Residual Cl- secretion, most likely due to the CFTR Cl- channel, was observed in 63% of subjects, more frequently in early chronically PA colonized than among late or not colonized patients. These results demonstrate the presence of some active F508del-CFTR in the apical cell membrane and imply that factors other than the CFTR-mediated residual Cl- secretion determine the age of onset of PA colonization.

Adolescent↗

Effect of prolonged subcutaneous implantation of peritoneal catheter on peritonitis rate during CAPD: a prospective randomized study.

We conducted a prospective randomized controlled study to confirm our earlier observation that prolonged subcutaneous implantation of peritoneal catheter reduced peritonitis rate when compared to retrospective data from patients with catheters placed by conventional access technique. A total of 60 patients were randomized into two groups: 30 patients had catheters left implanted subcutaneously for 6 weeks (I) and the other 30 patients had catheters inserted by conventional technique and had 6 weeks of break-in period (C). Subgroups of 15 patients each with new and conventional techniques used Y-connector (IY, CY) and remaining patients used standard spikes (IS, CS). Mean age was 47.7 years (range 16-71); 61.0% were male and 44.1% diabetics. Peritonitis, exit site infection, simultaneous peritonitis and exit site infection, and complication related to Staphylococcus or Pseudomonas infections were observed for up to 2 years in each patient after initiation of bag exchange or until termination of CAPD by transfer to hemodialysis or by death. Total duration of observation was 493.2 patient-months for new access technique and 409.6 patient-months for conventional technique. Patients in IY group had the lowest incidence of peritonitis (1/14.9 patient-months) and exit site infection (1/16.8 patient-months) among four subgroups. Peritonitis rate in IY was significantly lower compared to CY or CS. The total peritonitis-free period in those patients who did not experience peritonitis during the observation period was also significantly longer in IY (120 patient-months) than in CY (26 patient-months), IS (10.6 patient-months), or CS (10.4 patient-months). Simultaneous peritonitis and exit site infection was observed in none of IY group but 3 episodes in CY, 4 episodes in IS, and 3 episodes in CS. The rates of complications related to Staphylococcus aureus and Pseudomonas infections were also significantly lower in IY than in CY, IS, or CS. Technique survival did not differ between the two groups. The present results confirm our previous observation that the new access technique reduces the incidence of peritonitis probably by reducing infection via periluminal route. The Y-connector system further reduces peritonitis rate by reducing infection via intraluminal route.

Adolescent↗

Inflammatory responses of corneal epithelial cells to Pseudomonas aeruginosa infection.

PURPOSE: We hypothesized that corneal epithelium plays a role in the innate immune response by sensing the presence of pathogens and providing signals that activate the corneal defense system. We sought to determine the mechanisms involved in the activation of the signaling pathways and subsequent production of proinflammatory cytokines in human corneal epithelial cells (HCECs) in response to Pseudomonas aeruginosa infection. METHODS: Epithelial monolayers of a telomerase-immortalized HCEC line, HUCL, and primary cultures of HCECs were exposed to P. aeruginosa (PA01 strain) with or without the presence of the NF-kappaB inhibitor kamebakaurin, the p38 inhibitor SB203580, or the JNK inhibitor SP600125. IkappaB-alpha phosphorylation and degradation and p38 and JNK phosphorylation were assessed at different time points by Western blot analysis. Interleukin (IL)-6, IL-8, and TNF-alpha levels were determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Exposure of HUCL cells and primary HCECs to P. aeruginosa resulted in rapid activation of NF-kappaB as indicated by an increase in IkappaB-alpha phosphorylation observed within 15 min and by IkappaB-alpha degradation, which peaked in 1 hr. Two stress-activated mitogen-activated protein kinases, p38 and JNK, were also activated as their phosphorylation was induced by P. aeruginosa infection. Concomitant with the activation of these Toll-like receptor-mediated signaling pathways, transcriptional expression and subsequent secretion of IL-6 and IL-8 in HUCL cells were also induced by P. aeruginosa. Presence of the NF-kappaB inhibitor kamebakaurin in culture medium blocked P. aeruginosa-induced NF-kappaB activation and inhibited IL-6, IL-8, and TNF-alpha expression and secretion. Inhibition of p38 or JNK also resulted in a decrease in bacteria-induced expression and secretion of these cytokines. CONCLUSIONS: P. aeruginosa triggers an innate immune response in HCECs, and NF-kappaB and, to a lesser extent, the p38/JNK signal pathways are responsible for P. aeruginosa-induced proinflammatory cytokine production in these cells.

Anthracenes↗

Pseudomonas osteomyelitis of the metatarsal sesamoid bones.

It is unusual for osteomyelitis of the sesamoid bones to occur after a puncture wound to the foot. When the puncture occurs through tennis shoes, the risk of Pseudomonas infection is increased. Pseudomonas was the causative organism in 7 of 22 cases reported in the literature. This report will explore the causes and natural history, as well as the treatment, of these infections. Initially, basic wound care principles should be adhered to when treating these wounds. Patient awareness and close follow-up is important to ensure complete healing. Treatment of this case involved intravenous antibiotics and medial sesamoidectomy. Foot deformities can occur with sesamoid osteomyelitis and sesamoid excision. Hallux valgus deformity was noted to occur with the osteomyelitis and worsen with sesamoid excision. Preservation of surrounding structures during excision is important to prevent deformity.

Adolescent↗

Age-related susceptibility to Pseudomonas aeruginosa ocular infections in mice.

The susceptibility of newborn and infant mice to eye infection by Pseudomonas aeruginosa was studied in 5-, 10-, 15- to 16-, and 21-day-old mice. In the first of three age-related susceptibility experiments, inoculation of P. aeruginosa under the unopened eyelids of infant (5- and 10-day-old) mice in the absence of prior corneal wounding resulted in acute infection and rapid death of many of the animals. However, endophthalmitis was observed in about 30% of bacteremic animals that survived to age 14 to 15 days. In the second experiment, 15- to 16-day-old mice whose eyes were open received P. aeruginosa topically onto either wounded or unwounded corneas. At least 50% of the mice that received both corneal wounding and the bacteria exhibited keratitis, endophthalmitis, and subsequent phthisis bulbi. None of the infected mice died of bacteremia. In addition, mice infected in the absence of corneal wounding did not exhibit any eye damage. In the third experiment, the wounded-cornea responses of 21-day-old mice to P. aeruginosa were more variable. Thirty seven percent of the mice exhibited an intermediate response of decreased eye size and cataracts which was not observed in 15- to 16-day-old mice, 32% recovered spontaneously, and 29% exhibited complete shrinkage of the infected eyes. The variability of the latter responses may reflect a transitional maturation period of natural immunity to the organism in some of the animals, since all 4- to 6-week-old adult mice respond routinely to ocular wounding and similar infections with the organism by undergoing a spontaneous resolvable keratitis (3 to 4 weeks).

Aging↗

Bacteriophage Phi S1 infection of Pseudomonas fluorescens planktonic cells versus biofilms.

This communication focuses on the efficacy of a specific lytic phage, phage Phi S1, as a control agent of Pseudomonas fluorescens biofilms. The effect of phage infection temperature and the host growth temperature were evaluated. The results obtained showed that the phage infection process was temperature dependent and that the optimum temperature of infection of planktonic cells and biofilms was 26 degrees C. At this temperature, bacteriophage Phi S1, at a multiplicity of infection (MOI) of 0.5 infected both planktonic cells and biofilms causing a biomass reduction of about 85% in both cases.

Bacteriophages↗

Antineutrophil cytoplasmic autoantibodies (ANCA) in children with cystic fibrosis.

Anti-neutrophil cytoplasmic antibodies (ANCA) represent a useful diagnostic tool in patients with small vessel vasculitis. Circulating ANCA specific for bactericidal/permeability increasing protein (BPI) have been recently reported in adult patients with cystic fibrosis (CF), an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene with consequent impaired function of a transmembrane chloride channel. To contribute to the better understanding of the significance of ANCA in this disease, we investigated ANCA presence and antigenic specificity in children with CF. Results were correlated with clinical status, immunological data, age and genotype. The indirect immunofluorescence pattern of a total of 71 children with CF indicated that 31 were c-ANCA positive, while seven were p-ANCA positive. In further ELISA studies of ANCA antigenic specificity, 51 out of 66 investigated samples were positive for BPI, and 14 out of 28 were positive for proteinase 3 (PR3). We found an association between levels of antibodies against PR3 with age and Pseudomonas infection. We did not, however, find any correlation between CFTR genotypes, Pseudomonas infection or paediatric parameters and the level of anti-BPI antibodies. High positivity of anti-BPI antibodies were seen even among the youngest CF patients, before the development of clinical signs of CF, indicating that formation of ANCA might be a very early event in the disease. Both anti-BPI and anti-PR3 antibodies may play a significant, although variable role, in the pathogenesis of CF.

Adolescent↗

Preferential diaphragmatic weakness during sustained Pseudomonas aeruginosa lung infection.

Infection with Pseudomonas aeruginosa plays a major role in the pulmonary inflammation and injury associated with cystic fibrosis. Lung inflammation may also lead to more widespread systemic effects on other organs. We tested the following hypotheses: (1) ongoing P. aeruginosa lung infection produces diaphragmatic and limb muscle weakness and (2) such muscle dysfunction is directly correlated with the level of pulmonary inflammation. Chronic bronchopulmonary infection with mucoid P. aeruginosa was induced in C57BL/6 mice. At Day 2 after infection, diaphragmatic force was decreased (37%) only in mice infected with a high dose of 1 x 10(6) cfu, whereas by Day 7 after infection, diaphragmatic force was similarly reduced (36%) even at a fivefold lower inoculating dose. No significant correlations were found between diaphragmatic weakness and pulmonary inflammation, as assessed by the number of neutrophils, macrophages, and lymphocytes in bronchoalveolar lavage fluid. Moreover, in marked contrast to the diaphragm, no effects of P. aeruginosa infection on contractile function were observed in prototypical slow- and fast-twitch hindlimb muscles. We conclude that sustained lung infection with P. aeruginosa induces preferential weakness of the diaphragm, which is not directly correlated with the degree of pulmonary inflammation induced under these conditions.

Animals↗

Gender differences in cystic fibrosis: Pseudomonas aeruginosa infection.

The median survival age for females with cystic fibrosis (CF) is approximately 3 years younger than for males. We tested whether earlier acquisition of Pseudomonas aeruginosa (PA) by female CF patients or the greater impact of this organism on their lung disease, or both, contribute to their poorer survival. PA infection status, survival, pulmonary function tests, and chest X-ray scores from patients who were followed at our center for at least 2 years with a minimum of three respiratory cultures per year were analyzed (n = 848). The median age of chronic infection with mucoid PA was 1.7 years earlier in females than in males. Patients infected with mucoid PA had poorer survival, chest X-ray scores, and pulmonary function tests than patients who had either no Pseudomonas species or only the nonmucoid phenotype. Acquisition of mucoid PA was associated with an accelerated rate of decline in pulmonary function. However, the rate of change of pulmonary function after mucoid PA infection was similar for males and females. Moreover, even among patients who had only the mucoid form or only the nonmucoid form, males had better percent predicted forced expiratory volume in 1 sec and better survival. Therefore, factors in addition to earlier acquisition of mucoid PA may contribute to the poorer survival of female CF patients.

Adolescent↗

[Epidemiological study on nosocomial infection of Pseudomonas cepacia by plasmid analyses].

In order to clarify the usefulness of plasmid analyses in epidemiological study, plasmid DNA profiles, restriction fragment patterns of chromosomal DNA analysed by pulsed-field gel electrophoresis (PFGE), and patterns of extracellular products were performed in twenty-four nosocomial strains of Pseudomonas cepacia isolated at the Kagawa Medical School Hospital. Fifteen strains were obtained from 15 patients admitted in A ward, three strains were obtained from nebulizer devices used in A ward, 5 strains were obtained from 5 patients admitted in B ward, and 1 strain was obtained from a patient admitted in C ward. Three different patterns which differed from ward to ward were clearly distinguished by PFGE patterns and patterns of extracellular products. On the other hand, plasmid DNA profiles were different in some strains obtained from B ward. These results suggested that plasmid analyses combined with other typing methods are useful in more precise epidemiological analysis on nosocomial infection of P. cepacia.

Burkholderia cepacia↗

[Studies of dosing regimens and combination effects of aminoglycosides and beta-lactam in an experimental Pseudomonas aeruginosa infection in mice].

The optimal dosing regimens and combination effects of gentamicin (GM), or astromicin (ASTM) and piperacillin (PIPC) against P. aeruginosa in a mouse thigh infection model were studied. Therapeutic efficacy of the single regimen and duration of a postantibiotic effect (PAE) of GM and ASTM were dose dependent, but those of PIPC were dose independent. The optimal dosing of GM or ASTM with the same total daily dose was less frequent, but that of PIPC was frequent. Initial killing (the delta log bacteria changed at 2 hour after starting of the therapy) was the main significant pharmacokinetic and pharmacodynamic parameter determining efficacy for GM, whereas the time that serum levels exceeded the minimum inhibitory concentration (T greater than MIC) was the major parameter for PIPC. The optimal synergistic combinations of GM or ASTM plus PIPC in various dosing intervals with the same total daily dose were observed in the less frequent regimens of GM or ASTM and the frequent regimen of PIPC. The differences of therapeutic efficacy were observed in twice a day regimens of GM or ASTM plus PIPC in three dosing schedules (GM or ASTM before PIPC, with PIPC simultaneously, after PIPC). The effect of GM or ASTM after PIPC exposure was inferior to that of the other dosing regimens. These findings suggest that it may be possible to use the optimal regimens of aminoglycosides and beta-lactams against clinical P. aeruginosa infections in humans. Further careful, controlled clinical trials are needed.

Aminoglycosides↗