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T lymphocyte-mediated protection against Pseudomonas aeruginosa infection in granulocytopenic mice.

BALB/c mice immunized with Pseudomonas aeruginosa immunotype 1 polysaccharide develop protective T cell immunity to bacterial challenge. In vitro, T cells from immunized mice kill P. aeruginosa by production of a bactericidal lymphokine. The present study demonstrates that adoptive transfer of T cells from immunized BALB/c mice to granulocytopenic mice resulted in 97% survival on challenge with P. aeruginosa, compared with 17% survival with adoptive transfer of T cells from nonimmune BALB/c mice. This protection is specifically elicited by reexposure to the original immunizing antigen; adoptive recipients cannot withstand challenge with immunotype 3 P. aeruginosa. However, the adoptive recipients do survive simultaneous infection with both P. aeruginosa immunotypes 1 and 3. Adoptive transfer of T cells from the congenic CB.20 mice, which are unable to kill P. aeruginosa in vitro, provides only 20% protection to granulocytopenic mice. These studies indicate that transfer of specific immune T lymphocytes can significantly enhance the resistance to P. aeruginosa infection in granulocytopenic mice.

Agranulocytosis↗

Microbiological activity and clinical efficacy of a colistin and rifampin combination in multidrug-resistant Pseudomonas aeruginosa infections.

The aim of the study was to assess the microbiological activity and clinical efficacy of colistin and rifampin combination against multidrug-resistant (MDR) Pseudomonas aeruginosa infections. The antimicrobial activity of the colistin/rifampin combination was evaluated using the checkerboard and time-kill curve methods against different MDR P. aeruginosa strains. The combination of rifampin and colistin resulted fully (1 strain) or partially (5 strains) synergistic for 6/7 strains and minimum inhibitory concentrations (MICs) in combination were reduced to easily obtainable therapeutic levels. The time-kill curves showed that the combination was bactericidal against the strains tested. The clinical efficacy of the combination was tested in four patients with difficult-to treat infections (sepsis or pneumonia) caused by MDR P. aeruginosa. All infections were successfully treated. Our microbiological and clinical observations suggest that the addition of rifampin to colistin may result in a synergistic bactericidal combination that may be useful in patients with infections caused by MDR P. aeruginosa which are difficult to cure.

Adult↗

[Serodiagnosis of Pseudomonas aeruginosa infections in mucoviscidosis: comparative study of Western blotting, ELISA exotoxin A and ELISA phospholipase C].

Anti-Pseudomonas aeruginosa antibodies were studied by Western Blot, ELISA-exotoxin A and ELISA-phospholipase C for 91 serums from 31 patients with cystic fibrosis. More, for the two enzyme-linked immunosorbent assays, 44 serums from 44 healthy individuals were studied as controls. The study of these three parameters revealed the followings: with no infection by Pseudomonas aeruginosa all the results were negative, at the beginning of the infection, anti-exotoxin A antibodies appeared in first, followed in some cases by the reactions of Western Blot, anti-phospholipase C antibodies became positive at last and went on a par with the installation of the chronic characteristic of the infection, as soon as the chronicity were indisputable, the three methods revealed elevated serum antibodies amounts. Generally there was a correlation between detected antibodies and Pseudomonas aeruginosa isolation in sputum. Among these three methods, ELISA-exotoxin A appeared to be the most interesting because of its good reproducibility and its early positivity, before the others methods and sometimes before Pseudomonas aeruginosa isolation. It would be a significant argument to establish as soon as possible an antimicrobial therapy.

ADP Ribose Transferases↗

[A clinical study of chronic lower respiratory tract infections with Pseudomonas aeruginosa by transtracheal aspiration].

We investigated the yearly changes of the incidence of Pseudomonas aeruginosa (P. aeruginosa) isolated from chronic lower respiratory tract infections (CLRTI), and also performed a clinical study on CLRTI with P. aeruginosa by transtracheal aspiration (TTA) to clarify the recent trend of P. aeruginosa infection in CLRTI and the predisposing clinical factors to the acute exacerbation. The isolation rate of P. aeruginosa among the total isolated bacteria in CLRTI between December 1978 and March 1983 was 8.4%, but it increased to 23.1% between April 1988 and March 1993. In 69 episodes (40 cases) of P. aeruginosa isolated from CLRTI between April 1983 and March 1993, monomicrobial infections of P. aeruginosa were 42 episodes (60.9%) and polymicrobial infections were 27 episodes (39.1%). When the diseases were classified into acute exacerbated and non-exacerbated phases, polymicrobial infections were seen more in the former phase, and the principal organisms detected with P. aeruginosa were Haemophilus influenzae and Streptococcus pneumoniae. In the acute exacerbated cases, predisposing conditions concerning the exacerbation were divided into four patterns: 1. polymicrobial infections with H. influenzae or S. pneumoniae, 2. after acute upper respiratory tract infections due to viral superinfection, 3. early phase from bacterial replacement by P. aeruginosa, 4. immunocompromised states such as adrenal corticosteroid administration or systemic underlying diseases. These results suggest that the importance of P. aeruginosa in CLRTI is increasing year by year and we must pay attention to the fact that P. aeruginosa alone may also cause acute exacerbation in the latter 2 patterns of the condition.

Adult↗

[Choice of a rapidly bactericidal beta-lactamin-aminoglycoside combination in the treatment of Pseudomonas aeruginosa infections at a child intensive care unit].

Morbidity and mortality among children with Pseudomonas aeruginosa infection in Pediatric Intensive Care Unit remains high. Delays in bacterial killing may be responsible for the poor outcome. Antimicrobial sensitivity and timed-killing assays were determined for ticarcillin, azlocillin, piperacillin, cefsulodin, ceftazidime, gentamicin, tobramycin and amikacin alone and in combination against 40 strains of Pseudomonas aeruginosa isolated from blood cultures and tracheal aspirate. Antibiotic concentrations used were at clinically achievable level. None bactericidal effect was observed with each beta-lactamin alone. However with the combinations azlocillin or piperacillin or cefsulodin or ceftazidime plus amikacin a bactericidal effect was observed at 4.5 hours.

Aminoglycosides↗

Impaired ability of Cftr knockout mice to control lung infection with Pseudomonas aeruginosa.

The present study was aimed at investigating the innate susceptibility of C57BL/6-Cftrunc/Cftrunc knockout [B6-Cftr (-/-)] mice to pulmonary infection with Pseudomonas aeruginosa. Our results indicate that 58.4% of B6-Cftr (-/-) mice died within 6 d following lung infection with 10(5) P. aeruginosa entrapped in agar beads, whereas only 12.1% of B6-Cftr (+/+) mice died over the same period of time. Moreover, the number of bacteria recovered from the lungs of B6-Cftr (-/-) mice 3 and 6 d after infection was significantly higher than that observed in their littermate controls. No correlation was found between the weight or age of the animals and the number of viable bacteria recovered from the lungs of mice. Histopathological examination of lung sections from P. aeruginosa-infected mice revealed that the infection results in a severe bronchopneumonia. Both B6-Cftr (-/-) knockout mice and their littermate controls developed similar lung pathology during the course of infection. Overall, results reported in the present study suggest that a defect at the Cftr locus leads to an exacerbation of P. aeruginosa lung infection resulting in a dramatically increased mortality rate and higher bacterial load.

Animals↗

Does centralized treatment of cystic fibrosis increase the risk of Pseudomonas aeruginosa infection?

Two hundred and forty Danish patients with cystic fibrosis (97% of the total CF population in Denmark) participated in a point-prevalence study of Pseudomonas aeruginosa infection. One hundred and ninety-two patients were treated at the Danish CF centre and 48 patients were treated in other places. The age distribution was significantly different as no patients older than 19 years were found in the non-centre group. Pathogenic bacteria were isolated from the sputum of 96% of the patients. P. aeruginosa was more prevalent in patients from the centre, whereas Staphylococcus aureus was more prevalent in the non-centre group. No difference in serogroup and phage pattern of P. aeruginosa was found. There was a tendency that non-centre treated patients acquired chronic broncho-pulmonary P. aeruginosa infection later, but at the age of 16 years 90% of all patients will be chronically infected. Chronic P. aeruginosa infection was significantly more common in the age group 10-14 years at the centre than outside the centre. It is not possible to prevent chronic P. aeruginosa infection in CF patients treated in small groups and because of the better prognosis of centralized treatment the latter must be recommended.

Adolescent↗

[A control study on bacterial resistance and clinical features of lower respiratory tract infection with Pseudomonas aeruginosa in medical intensive care unit and general ward].

OBJECTIVE: To compare the bacterial resistance and clinical features of lower respiratory tact infection with Pseudomonas aeruginosa (PA) in medical intensive care units (MICU) and general wards (GW) and to analyze the predisposing factors to PA infection. METHODS: Three hundred and twenty three patients with lower respiratory tract PA infection, aged from 30 to 91 years, admitted into Shanghai Zhongshan hospital from May 1997 to December 2001 (163 in MICU and 160 in GW) were included in this retrospective study. The predisposing factors, underlying diseases, clinical presentations, laboratory data, treatment and outcome of these patients were analyzed. On the other hand, the susceptibility patterns to antibiotics of 1 387 PA strains (879 from MICU and 508 from GW) from the recorders of the bacteria culture chamber were investigated. RESULTS: The underlying diseases of the patients mainly were chronic obstructive pulmonary disease (23.3% of patients in MICU and 12.5% in GW) and malignant tumor (14.7% in MICU and 14.4% in GW). A relatively high resistant rates of PA strains to common antibiotics were found in both groups: cefoperazone/sulbactam 1.0% (MICU: 1.0%, GW: 1.1%), piperacillin/tazobactam 2.5% (MICU: 1.0%, GW: 5.0%), amikacin 6.1% (MICU: 7.0%, GW: 4.5%), ceftazidime 9.2% (MICU: 11.6%, GW: 2.7%), cefepime 11.3% (MICU: 12.2%, GW: 10.8%), imipenem 13.5% (MICU: 6.8%, GW: 25.2%), piperacillin 13.8% (MICU: 17.8%, GW: 6.9%), cefoperazone 16.4% (MICU: 22.1%, GW: 6.6%), ticarcillin/clavulanic acid 17.2% (MICU: 21.2%, GW: 17.3%), cidomycin 18.5% (MICU: 20.5%, GW: 14.9%), ciprofloxacin 20.2% (MICU: 27.2%, GW: 8.1%), ceftriaxone 44.4% (MICU: 53.6%, GW: 28.4%). Most of the resistant rates of strains from MICU were higher than those from GW. The susceptibilities of PA to ceftazidime and piperacillin changed little during the past 5 years and were above 80.00%. Since 1988, especially from 2000, the susceptibility of PA to most antibiotics became remarkably lower. With selected antibiotic treatment of the infections 196 patients were cured, 79 patients died in hospital. The mortality of patients in GW (16.25%, 26/160) was lower than that in MICU (32.52%, 53/163). CONCLUSION: Precautions to PA infection is important in patients with predisposing factors. Patients with Lower respiratory tract PA infection in MICU had different clinical features, laboratory data and outcome compared to GW patients. The PA isolated from MICU patients had a higher resistant rate to many antibiotics than that from GW patients. It is important to perform antibiotic sensitivity test timely to help correct selection of drugs, especially for MICU patients.

Adult↗