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[Ofloxacin in the treatment of Pseudomonas aeruginosa infections of the ear].

Twenty-three patients suffering from a Pseudomonas infection of the ear were treated with ofloxacin in a prospective study. The type of infection was as follows: external otitis 4, external otitis with furuncle 3, external otitis and otitis media 5, acute exacerbation of chronic otitis media 7, infection of radical mastoidectomy 3, malignant external otitis 1. All patients had previously been unsuccessfully treated elsewhere. The average period of infection was 13.7 days. The patients received 200 mg of ofloxacin (Tarivid) twice daily for 3 weeks. At the same time the ear was cleaned by suction at 2-4 day intervals and a Normison ear strip applied. Twenty patients were completely cured, 2 patients stopped taking ofloxacin early as a result of improved symptoms but their condition subsequently deteriorated. After a further 3 weeks of consistent treatment both of the cases were also cured. Hence only one patient did not respond to our therapy; that is a success rate of 95%. These results are compared with those of our former therapeutic plan in which all patients with resistant Pseudomonas ear infections were treated as in-patients with selected intravenous antibiotics.

Adult↗

Pseudomonas aeruginosa infections of the skin.

Otitis externa, green nail syndrome, toe web infections, hot tub folliculitis, superinfections in chronic antibiotic-treated acne and infectious eczematoid dermatitis are examples of mild cutaneous infections due to Pseudomonas aeruginosa. These may occur in otherwise healthy persons. In persons with lowered resistance, more severe infections such as malignant otitis externa, blastomycosis-like pyoderma and necrotizing fasciitis are observed. Ecthyma gangrenosum, the pathognomonic skin sign of Pseudomonas septicemia, occurs in debilitated or terminally ill patients and must be treated immediately.

Acne Vulgaris↗

Reduced resistance to Pseudomonas septicaemia in diabetic mice.

Antibacterial resistance in a diabetic state was studied using experimental Pseudomonas infection in streptozotocin (SZ) induced diabetic mice. The results obtained were as follows: (1) there was no difference in acute death rate between normal and diabetic mice when infected with Pseudomonas aeruginosa. However, a significant increase in the number of bacteria in the kidney and liver occurred at a later stage of infection in diabetic mice. (2) Active immunization with a phenolized vaccine resulted in 100% survival in either normal or diabetic mice; otherwise challenge was lethal. However, the organs examined in diabetic vaccinated mice contained distinctly increased numbers of bacteria as compared with normal vaccinated mice 7 days after infection. (3) There were no significant differences in antibody titre between normal and diabetic ice after infection, but passive protection with immune serum from diabetic vaccinated mice was less effective than that from vaccinated mice. Furthermore, immune serum from normal vaccinated mice exerted protective action less efficiently in diabetic recipients than in normal recipients. (4) The bactericidal effect of peripheral whole blood was apparently lower in diabetic mice than in normal mice. (5) Treatment with insulin restored such reduced resistance to Pseudomonas infection in diabetic mice. These findings suggest that the decreased resistance to Pseudomonas infection in diabetic mice should be ascribed to impaired function of antibody, abnormalities in phagocytic cells and disturbed microcirculation caused by the insulin-deficient state.

Animals↗

[Use of azlocillin in the treatment of Pseudomonas bronchopulmonary infections].

Eleven patients with severe bronchopulmonary infection due to Pseudomonas were treated with azlocillin in doses of 250 mg/kg/day. Severe preexisting respiratory diseases, such as bronchopulmonary carcinoma, bronchiectasis or respiratory insufficiency were present in all cases. All patients had been unsuccessfully treated with various antibiotics before they received azlocillin. The pathogenicity of the isolates was assessed by germ counts in sputum. Comparative in vitro sensitivities to carbenicillin and azlocillin were determined by the disc method and by measurement of the minimum inhibitory concentrations in liquid medium. All strains of Pseudomonas aeruginosa isolated were sensitive to azlocillin with minimum inhibitory concentrations of 0.5 to 64 micrograms/ml. When tested against carbenicillin, 4 of the strains were resistant and 1 had intermediate sensitivity. The carbenicillin/azlocillin minimum inhibitory concentrations ratio was usually equal to 4. Clinical results were satisfactory in 7 cases; inadequate response or failure was observed in 4 cases and attributed to the replacement of Pseudomonas by another pathogen (Proteus morganii or Klebsiella pneumoniae). This study suggests that azlocillin is of value in the treatment of bronchopulmonary infections caused by Ps. aeruginosa.

Adult↗

Experimental urinary tract infection with Pseudomonas aeruginosa in mice.

Urinary tract infection with Pseudomonas aeruginosa was induced in mice by transurethral inoculation of the organism into the bladder, followed by urethral obstruction for 6 h. The infection was mostly localized in the urinary organs. P. aeruginosa P9 was selected as the challenge organism from 10 laboratory strains of P. aeruginosa. After the inoculation of 10(7) colony-forming units of P. aeruginosa P9, transient bacteremia was observed in some of the mice from 6 h to 1 day after the inoculation. The number of organisms in the bladder tissue gradually decreased, whereas that in the kidneys increased to levels of 10(6) to 10(7) colony-forming units in 3 days, and these levels remained up to 2 weeks after the inoculation. The organisms gradually disappeared thereafter, and spontaneous recovery took place. The organisms could be recovered from the kidneys of 95% of the mice, and the gross lesions in the kidneys were observed in 77% of the mice 1 week after inoculation. The method developed here is simple and may be useful in the study of urinary tract infections due to P. aeruginosa and other species of bacteria.20

Animals↗

Pseudomonas aeruginosa infection in hospital: a comparison between 'infective' and 'environmental' strains.

One hundred and fifty-six infections or episodes of infection associated with Pseudomonas aeruginosa in six hospitals over 14 months were investigated. Pyocine typing and serotyping suggested that 145 distinct episodes had occurred, caused by 78 different strains. During this period 15 distinct strains were isolated from the environment at one of the hospitals; 12 of these were apparently unassociated with infection in the same ward during the period, and 4 were of types not encountered in infective processes at any hospital. There appeared to be a rather higher proportion of unclassifiable pyocine inhibition patterns among the environmental strains; in general these strains also produced smaller amounts of haemolysin. If failure to produce haemolysin in vitro is correlated with lack of virulence in vivo, this may partially explain the sporadic nature of hospital infection with Ps. aeruginosa, despite the prevalence of strains of this species in the environment.

Child↗

ENT manifestations of Pseudomonas aeruginosa infection in HIV and AIDS.

In acquired immunodeficiency syndrome (AIDS), opportunistic infections occur which are usually related to defects in cell-mediated immunity. However, there has also been an increase in the incidence of bacterial infections in this population, including infections caused by Pseudomonas species. This study reveals the wide range of ear, nose and throat manifestations which can be caused by Pseudomonas aeruginosa in patients with HIV and AIDS and illustrates the need for a high index of clinical suspicion combined with accurate microbiological data for treating these potentially life-threatening infections. In addition, treatment using combination chemotherapy, such as ciprofloxacin and ceftazidime, is advised, as it has been shown that dual therapy results in a significantly lower mortality.

AIDS-Related Opportunistic Infections↗

Endemic Pseudomonas aeruginosa infection in a neonatal intensive care unit.

BACKGROUND: Nosocomial infections due to Pseudomonas aeruginosa have been well described, but the environmental reservoir of the organism varies. We conducted an epidemiologic and molecular investigation of endemic P. aeruginosa infection among infants in a neonatal intensive care unit that was associated with carriage of the organisms on the hands of health care workers. METHODS: In August 1998, colonization or infection with P. aeruginosa was identified in six infants. Surveillance cultures for P. aeruginosa were obtained from the other 27 infants in the unit, and possible environmental reservoirs were also assessed. The hands of health care workers were inspected and cultured, and risk factors for P. aeruginosa colonization were evaluated. Isolates were analyzed for clonality by pulsed-field gel electrophoresis. RESULTS: Surveillance cultures showed that three additional infants were colonized with P. aeruginosa. Cultures of environmental specimens were negative, but cultures of the hands of 10 of 165 health care workers (6 percent) were positive for P. aeruginosa. Increasing age (P=0.05) and a history of the use of artificial fingernails or nail wraps (P=0.03) were both risk factors for colonization of the hands. From January 1997 to August 1998, 49 infants were infected or colonized with P. aeruginosa. Pulsed-field gel electrophoresis demonstrated that 17 of these infants and 1 health care worker who had onychomycosis had the same clone. Infants who were exposed to this health care worker in August 1998 were at greater risk of having this clone than infants who were not exposed to this health care worker (odds ratio, 41.2; 95 percent confidence interval, 1.8 to 940.0; P=0.006). CONCLUSIONS: An increased rate of infection and colonization with P. aeruginosa among infants in neonatal intensive care units should be investigated by assessing potential reservoirs, including environmental sources as well as patients and health care workers.

Bacterial Typing Techniques↗

Antibiotic therapy for chronic infection of pseudomonas in the lung.

Chronic Pseudomonas aeruginosa lung infection is an endobronchiolitis characterized by the microcolony mode of growth (biofilm). Early colonization is treated with oral ciprofloxacin combined with colistin inhalation. Chronic infection is treated with "maintenance chemotherapy" consisting of beta-lactam antibiotics and tobramycin intravenously in combination with colistin inhalation four times yearly.

Anti-Bacterial Agents↗

Rationale for development of immunotherapies that target mucoid Pseudomonas aeruginosa infection in cystic fibrosis patients.

Despite a complex sputum bacteriology, the progressive decline in pulmonary function that is the hallmark of the genetic disease cystic fibrosis (CF) is attributable to a single infecting pathogen, mucoid Pseudomonas aeruginosa. Therefore, active and passive immunotherapies that target this particular variant of the bacterium should be of value in attenuating infection and interfering with the decline in pulmonary function. The major surface antigen of mucoid P. aeruginosa is referred to as either mucoid exopolysaccharide (MEP) or alginate, a random polymer of D-mannuronic and L-guluronic acid residues linked beta 1-4. During chronic infection CF patients make antibodies to MEP that fail to mediate opsonic killing of bacteria in vitro. These antibodies can be elicited by vaccination in 35-40% of plasma donors given a preparation of MEP comprised of only the highest molecular-weight polymers; inclusion in human vaccines of smaller polymers normally produced by the bacterium fails to elicit opsonic antibodies, just like in infected CF patients. Opsonic, but not non-opsonic, antibodies to MEP protect animals against chronic endobronchial infection. CF patients do produce opsonic antibodies to mucoid P. aeruginosa that are in a planktonic or suspended state, but these antibodies are not directed at the MEP antigen and they fail to kill P. aeruginosa growing in a biofilm. This is the state that the bacteria grow in the lung. Therefore immunoglobulin G preparations with opsonic antibodies to MEP could provide CF patients with antibodies that they normally do not produce during chronic lung infection and may improve their clinical course.

Animals↗

Effects of airway infection by Pseudomonas aeruginosa: a computed tomographic study.

BACKGROUND: Pseudomonas aeruginosa commonly infects the airways of patients with bronchiectasis. A study was undertaken to examine the relationship between infection of the airways with this pathogen, the morphological pattern of bronchiectasis on thin section computed tomographic (CT) scanning, symptom duration, smoking habits of the patients, and the presence of airflow obstruction. METHODS: Thin section CT scans of 22 adult patients with bronchiectasis and concurrent sputum infected by P aeruginosa (Pa +ve) and those of 45 randomly selected patients not infected by P aeruginosa (Pa -ve) were analysed independently by two thoracic radiologists. Patients with cystic fibrosis were excluded. Each scan was scored at a lobar level for extent of bronchiectasis, severity of bronchial wall thickening and dilatation, predominant pattern of bronchiectasis, presence of mucus plugging, and degree of decreased attenuation of the lung parenchyma. RESULTS: The Pa +ve group had more extensive bronchiectasis and a greater degree of bronchial wall thickening and dilatation on the CT scan than the Pa -ve group; more extensive decreased attenuation was seen in the Pa +ve group. These findings were robust on multivariate analysis; decreased attenuation was also independently related to the duration of sputum production. CONCLUSION: Patients with bronchiectasis infected by P aeruginosa have more extensive and severe bronchiectasis on thin section CT scanning than those without P aeruginosa infection. The bronchi and small airways are both involved, reflecting the end result of complex interactions between host airways and the numerous virulence factors produced by P aeruginosa.

Adult↗

[The spectrum of bronchopulmonary infection caused by Pseudomonas aeruginosa in patients infected with the human immunodeficiency virus].

OBJECTIVE: To describe the clinical spectrum of bronchopulmonary infections caused by Pseudomonas aeruginosa in patients infected with HIV. METHODS: A retrospective study of cases with P. aeruginosa pneumonia and tracheo-bronchitis in patients infected with HIV, diagnosed over a 5-year period (January 1990-December 1994) in a third level university hospital. RESULTS: Seven patients with pneumonia and 15 with tracheobronchitis were identified, with a mean age of 33 years. All patients were in an advanced stage of immunosuppression (median CD4 count 11/mm3) and 21 (95%) had AIDS. In 6 cases (86%) pneumonia was acquired in the community and no patient had severe neutropenia. Clinical presentation ranged from severe pneumonia with respiratory insufficiency and shock to subacute less severe disease. Two patients (29%) died in the first episode as a result of pneumonia. The combination of cough, purulent expectoration and fever was the usual presenting form of tracheo-bronchitis. Nine out of the 15 patients (60%) had been treated previously because of tracheo-bronchitis and/or bacterial pneumonia episodes not caused by P. aeruginosa. Twelve patients required hospital admission; ten patients (83%) because of tracheo-bronchitis symptoms. The initial response to therapy was satisfactory, but 12 (80%) relapsed, with 2.6 relapses per patient after a mean follow-up of 7.4 months. CONCLUSIONS: P. aeruginosa bronchopulmonary infections emerge in late stages of HIV disease. P. aeruginosa should be considered in the differential diagnosis of every patient with pneumonia and advanced AIDS, even in the absence of the traditionally reported risk factors. Initially, tracheo-bronchitis responds well to therapy, but its management is difficult because of the frequent relapses and the development of antibiotic resistance.

Adult↗

Piperacillin and tobramycin in the treatment of Pseudomonas lung infections in cystic fibrosis.

Fourteen children with cystic fibrosis and pulmonary lung infection due to Pseudomonas aeruginosa were treated with piperacillin (300 mg/kg/day) alone or piperacillin and tobramycin (7 mg/kg/day) iv. The outcome with respect to clinical state, chest X-ray and lung function tests was better with combination therapy than with piperacillin alone. Bacteriological response was the same with both regimens: leucocyte content of the sputum decreased, non-mucoid Ps. aeruginosa strains were eliminated, but mucoid strains were only suppressed (11 children). Peak serum levels of piperacillin averaged 102 mg/l, the overall serum elimination was 0.75 h and the mean sputum concentrations ranged from 1.07 to 2.2 mg/l. Peak serum levels of tobramycin averaged 5.15 mg/l, the half life was 1.25 h and the mean sputum concentrations ranged from 0.57 to 0.68 mg/l. The clearance of piperacillin and tobramycin was increased significantly. Drug-resistance did not develop during therapy.

Adolescent↗

Immediate and prolonged clinical efficacy of ceftazidime versus ceftazidime plus tobramycin in chronic Pseudomonas aeruginosa infection in cystic fibrosis.

20 patients with cystic fibrosis and chronic bronchopulmonary infection due to Pseudomonas aeruginosa entered a randomized cross-over study comparing ceftazidime (150 mg/kg body weight/24 h) plus tobramycin (10 mg/kg body weight/24 h) to ceftazidime alone (150 mg/kg body weight/24 h), both given intravenously for 2 weeks. 17 patients completed the study; both treatment regimens improved lung function and decreased the WBC count. No difference in clinical efficacy was found between the treatments. Pulmonary function returned to pre-treatment levels 3 months later with no difference between the treatments. No changes were seen in minimal inhibitory concentrations during treatment. None of the patients developed hypersensitivity or experienced serious adverse reactions to the drugs.

Adult↗

[Chemotherapy of Pseudomonas aeruginosa infections in children during the first three months of life].

The data on the efficacy of antibacterial drugs and their combinations in treatment of 150 three-month old infants with generalized infection due to Pseudomonas aeruginosa are presented. The clinical isolates of P. aeruginosa were found to be carriers of multiple drug resistance which markedly complicated the chemotherapy. Only combined antibacterial therapy of such infants proved to be rational. High activity of aminoglycosides, azlocillin and cefotaxime against P. aeruginosa and the synergistic action of their combinations observed in the patients permitted to recommend the use of combinations of the above drugs in the empirical chemotherapy.

Aminoglycosides↗

Phases of the serological response in Pseudomonas aeruginosa infections.

Sixty-four infections due to Pseudomonas aeruginosa in patients of a respiratory intensive care unit were studied. The length of serologically latent period following the appearance of P. aeruginosa decreased with the growing severity of the infection, however, the longest latent period occurred in lethal cases. As the phase of development of peak anti-LPS antibody titres was constant in each group, in fatal infections the serological response developed too late when sepsis had already started. The duration of the persistence of peak titres was also stable. In consequence of a close negative correlation between these two latter parameters, the period from the onset of antibody increase till the beginning of decrease was especially constant, independent of the severity of infection, the duration of the antigenic stimulus and the intensity of the serological response. The rate of decrease was an another stable value. All these refer to an endogenous, time-dependent regulation which, despite existing clinical symptoms and the presence of P. aeruginosa, starts anti-LPS antibody level to decline. Pseudomonas carrier state in convalescence was observed in cases with prolonged persistence of peak titre and with a lower rate of titre decrease.

Antibodies, Bacterial↗

Pseudomonas aeruginosa biofilm-deficient mutants undergo parallel adaptation during chronic infection.

Pseudomonas aeruginosa readily adapts to infection by acquiring stable and heritable mutations. Previously, we discovered that the first adaptations in a porcine wound model were rugose small-colony variants (RSCVs) caused by mutations in the wsp operon. These mutants overproduce Pel and Psl biofilm exopolysaccharides that improve defense against host responses. To identify other mechanisms of host adaptation that lead to hyperbiofilm phenotypes, we created a mutant with an activated wsp pathway but unable to produce these exopolysaccharides (ΔwspFΔpelAΔpslBCD). Porcine wounds were infected with this mutant and biopsies were sampled at days 7, 14 and 35. Small colony variants were isolated from the wound, and whole genome sequencing revealed these variants had acquired mutations in genes in lipopolysaccharide and type IV pili biosynthesis, with wzy and pilU genes being most commonly targeted. pilU mutants were associated with a hyperbiofilm phenotype that outcompeted the parental strain, and wzy mutants were associated with a hyperbiofilm phenotype and increased tolerance to host antimicrobial products. We further identified that several variants had acquired large genome deletions that spanned up to 320 consecutive genes and other variants with high copy numbers of Pf6 filamentous phage. Together our results suggest that the hyperbiofilm phenotype is adaptive in chronic infections and that P. aeruginosa has redundant and diverse pathways to generate this phenotype.

adaptation↗