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Comparative efficacy of ciprofloxacin, azlocillin, and tobramycin alone and in combination in experimental Pseudomonas sepsis.

Ciprofloxacin, azlocillin, and tobramycin, used alone and in combination, were studied in a model of lethal pseudomonas sepsis in rats. Ciprofloxacin alone at all doses studied and tobramycin alone at the highest dose reduced mortality significantly compared with saline controls. In contrast, survival was not improved with either azlocillin alone at all doses studied or lower doses of tobramycin alone. The combination of ciprofloxacin and azlocillin was synergistic in rats with systemic pseudomonas infection. Ciprofloxacin was rapidly absorbed, and effective levels persisted for 1-4 hr relative to the dose administered. These data suggest that ciprofloxacin may be a potent agent, either alone or in combination with azlocillin, in the treatment of severe pseudomonas infections.

Animals↗

Continuous beta-lactam antibiotic therapy in a double-lung transplanted patient with a multidrug-resistant Pseudomonas aeruginosa infection.

BACKGROUND: It is well known that the bactericidal effect of beta-lactam antibiotics is closely related to the time which the serum concentration of the antibiotic remains above the minimal inhibitory concentration of the target pathogen. Thus, the optimal administration of beta-lactam antibiotics would be the continuous infusion of the drug. METHODS: We present a case report with a critically ill double-lung transplanted patient with pneumonia due to a multidrug-resistant Pseudomonas aeruginosa who received continuously 8 g meropenem/24 hr. Based on a previous pharmacokinetic study showing that continuous infusion of meropenem is at least equivalent to intermittent administration this case report is reported to demonstrate the clinical efficacy of continuous infusion. RESULTS: C-reactive protein and pneumonia decreased rapidly when clinical conditions were improved significantly. Continuous administration of meropenem did not interfere with cyclosporine, no side effects were seen, and the patient's renal function was not impaired during the whole period of treatment. CONCLUSION: The continuous administration of beta-lactam antibiotics is a powerful application in critically ill patients to intensify antimicrobial therapy.

Anti-Bacterial Agents↗

Early cytokine and chemokine gene expression during Pseudomonas aeruginosa corneal infection in mice.

Using a multiprobe RNase protection assay, we examined cytokine and chemokine mRNAs that were expressed after corneal infection with Pseudomonas aeruginosa in mice. Cytokines that were upregulated included interleukin-1alpha (IL-1alpha) and -1beta, IL-1 receptor antagonist, IL-6, IL-11, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, stem cell factor, lymphotoxin beta, transforming growth factor beta1, and tumor necrosis factor alpha. Chemokine transcripts that were upregulated included Eotaxin; gamma-interferon-inducible protein 10; monocyte chemoattractant protein 1; macrophage inflammatory proteins 1alpha, 1beta, and 2; and RANTES. Peak expression of these cytokines and chemokines was observed between 1 and 3 days after infection. These responses returned to or approached baseline preinfection levels by 7 days after ocular challenge. Identification of the various cytokines and chemokines upregulated during corneal infection provides important information relevant to unraveling the pathogenesis induced by this bacterium and provides hope that specific molecules can be targeted for therapy.

Animals↗

[The therapeutic use of diucifon-activated immunocytes in adoptive transfer in mice with burn trauma complicated by Pseudomonas aeruginosa infection].

The effectiveness of the therapeutic use of diucyphone-stimulated syngeneic spleen cells was studied in mice with a burn trauma complicated by P. aeruginosa infection. For this purpose CBA mice were subjected to a burn of degree IIIa, covering 30% of their body surface, the wound was infected with P. aeruginosa strain, and 24 hours later spleen cells were taken from some of these animals. The spleen cells, incubated for 3 hours with or without diucyphone at a concentration of 10-100 micrograms/ml, were washed and reinfused intravenously to the remaining animals. The injection of diucyphone-treated spleen cells was shown to greatly increase the survival rate of the animals, to accelerate healing processes and to enhance the proliferative response of spleen cells to mitogens (phytohemagglutinin, concanavalin A) and interleukin-2. A conclusion was made on the efficacy of the therapeutic use of diucyphone-activated immunocompetent cells in cases of immunodeficiency induced by burn infection.

Adjuvants, Immunologic↗

Mercaptoethylguanidine inhibits the inflammatory response in a murine model of chronic infection with Pseudomonas aeruginosa.

Chronic airway inflammation induced by Pseudomonas aeruginosa is the eventual cause of respiratory failure in most people affected by cystic fibrosis. Recent evidence implicates the involvement of free radical and oxidant stress in the pathogenesis of the inflammatory injury. Here we report the efficacy of a novel experimental therapeutic, mercaptoethylguanidine (MEG), which has combined actions as a selective inhibitor of the inducible nitric oxide synthase and as a scavenger of peroxynitrite, a potent oxidant formed in the reaction of nitric oxide and superoxide radical. Chronic pulmonary infection was established in FVB/N mice by intratracheal administration of 10(5) colony-forming units of P. aeruginosa in agar beads. Treatment with MEG (10 mg/kg/dose every 8 h i.p.) inhibited weight loss in the first 3 days and reduced histologic injury at 8 days postinfection. MEG also reduced myeloperoxidase activity, a marker of neutrophil infiltration, at 8 days and concentrations of the proinflammatory cytokines interleukin-1beta, tumor necrosis factor-alpha, and macrophage inflammatory protein 2 in whole lung homogenates. MEG-treated animals and controls had similar perioperative mortality and comparable colony counts of P. aeruginosa at 8 days, indicating that MEG did not exacerbate infection. Our data suggest that MEG may be an effective immunomodulatory therapy of pulmonary inflammation induced by chronic infection.

Anesthesia↗

Pseudomonas eye infections in cyclophosphamide-treated mice.

Swiss-Webster mice challenged intracorneally with varying doses of P. aeruginosa exhibit eye infection within 24 hr. as detected by corneal opacity. The infection remains localized and spontaneously heals within 4 to 6 weeks. However, when mice are pretreated with a single i.p. injection of cyclophosphamide 4 days prior to either intracorneal or anterior-chamber challenge with various bacterial cell suspensions (10(1) to 10(8)), 83% of the anterior chamber and 54% of the intracorneally challenged mice (most at higher dilutions of the bacteria) died of Pseudomonas septicemia within 48 hr. Corneal damage was histochemically and ultrastructurally observed in surviving animals by 24 to 48 hr. following challenge by either route.

Animals↗

Nosocomial Pseudomonas cepacia infection associated with chlorhexidine contamination.

During the period of January to July 1980, a marked increase in the number of Pseudomonas cepacia isolates was observed in a microbiologic surveillance program. Although P. cepacia was isolated from wound specimens and vaginal cultures, the majority of isolates were of urinary origin from catheterized patients. Retrospective chart analysis of the patients failed to verify a causal pathogenic role for P. cepacia. However, fulminant sepsis subsequently developed in two hospitalized immunocompromised patients, with both blood and urine cultures positive for P. cepacia. Investigation revealed the presence of this organism in chlorhexidine (0.2 percent) mouthwash as well as other chlorhexidine antiseptic solutions used for routine urologic and obstetric procedures. The source of the P. cepacia was identified as the rubber tubing in the pharmacy through which deionized water passed during the dilution of concentrated (5 percent) chlorhexidine gluconate. In vitro tests demonstrated that P. cepacia was resistant to 0.2 percent chlorhexidine.

Aged↗

Localization of endovascular infection by selective catheterization with serial cultures.

Pseudomonas infection developed at the suture line of an aortic graft in a patient 13 years after the operation. The site of the infection was localized by quantitative blood cultures taken with the aid of selective arterial catheterization. This technique may be of great help in localizing the source of endovascular infection in difficult cases.

Aorta, Abdominal↗

Pseudomonas pickettii infections in a paediatric oncology unit.

Over a 3-month period, seven patients in a paediatric oncology unit developed Pseudomonas pickettii septicaemias. The outbreak was difficult to recognize since the cases occurred at widely spaced intervals and problems were experienced with the identification of the isolates. Many of the isolates were initially misidentified on the basis of a short sugar set used in the laboratory for identification of the non-fermenting Gram-negative bacilli. Moreover, the organisms had varying sensitivity patterns. The source of the organisms proved to be vials of 'sterile' distilled water which had been used for flushing the patients' indwelling Hickman lines. No further cases occurred once the use of this water was discontinued.

Child↗

[Efficacy and reversible nephrotoxicity of cefsulodin during treatment of septicemia from Pseudomonas aeruginosa infection of a pacemaker].

A case of P. aeruginosa septicaemia originating from a pace-maker electrode is described. Cure was obtained by surgical ablation of the contaminated electrode by a right thoracotomy and monotherapy with cefsulodin, an antibacterial agent. Nephrotoxicity was observed during treatment and regressed after its withdrawal. No other potentially nephrotoxic drug was used. The therapeutic indications of new beta-lactamase stable cephalosporins are reviewed.

Acute Kidney Injury↗

Isolation and treatment of cystic fibrosis patients with lung infections caused by Pseudomonas (Burkholderia) cepacia and multiresistant Pseudomonas aeruginosa.

Cross-infection with Pseudomonas aeruginosa and Pseudomonas cepacia has been shown sometimes to occur between cystic fibrosis (CF) patients in some CF centres, in some summer camps and during some social contacts between CF patients. Cohort isolation and improved hygienic precautions, however, have successfully been employed in some CF centres resulting in a decrease or elimination of cross-infection. Chronic P. aeruginosa infection is in most CF patients preceded by a period of intermittent colonization. Early aggressive chemotherapy (oral ciprofloxacin and nebulized colistin for 3 weeks) every time P. aeruginosa is detected in sputum has significantly decreased the incidence of new chronic infection in CF patients. Chronic P. aeruginosa infection can be treated by "maintenance chemotherapy" (= chronic suppressive chemotherapy). The principle is to restore lung function repeatedly by regular 2-week courses of intensive intravenous treatment every 3 months in the CF centre and adding daily inhalations of colistin between the courses, and sometimes also by giving oral ciprofloxacin during these intervals to unstable patients. Eradication of P. cepacia infection is virtually never obtained by antibiotic treatment with, e.g., ceftazidime and tobramycin or co-trimoxazole. Chronic suppression with doxycyclin or co-trimoxazole may give rise to some improvement in the clinical symptoms.

Adolescent↗

[Therapeutic effectiveness of gentamycin and rifampicin in experimental staphylococcal-Pseudomonas aeruginosa infection and their effect on immunological processes].

The survival level of the experimental animals with infection caused by Staphylococcus and Ps. aeruginosa was the highest when the animals were treated with a combination of gentamicin and rifampicin as compared to the use of every antibiotic alone. The combination had a more favourable effect on the plasmocytic reaction and production of the antibody-forming cells in the lymphoid organs which correlated with the therapeutic efficacy of the antibiotics.

Animals↗

[Topical administration of cefsulodin in postoperative Pseudomonas aeruginosa infection of the middle ears].

The clinical evaluation for cefsulodin (CFS) against P. aeruginosa was studied in postoperative infections of chronic otitis media by means of washing the middle ear with the drug, and the following results were obtained; CFS treatment was given to 5 cases, and the clinical responses were excellent in 4 and good in 1 case. P. aeruginosa in otorrhea was eradicated within several days, and otorrhea disappeared in all the cases. No side effect was observed in all cases.

Administration, Topical↗

[The protective effect of preparations made from plant seedlings in experimental Pseudomonas aeruginosa infection].

The influence of preparations obtained from oat and wheat seedlings (immunostimulating factors IF-1 and IF-2, respectively) on the natural resistance of mice to P. aeruginosa infection was studied. IF-1 and IF-2 were introduced intraperitoneally in a single injection in doses of 100 micrograms and 1000 micrograms per mouse 2 and 7 days prior to the inoculation of P. aeruginosa strain 8 in doses of 1 and 10 LD50. The presence of substances capable of stimulating the immunobiological reserves of the body in actively growing plants (seedlings) was shown.

Adjuvants, Immunologic↗

Effects of a human antiflagellar monoclonal antibody in combination with antibiotics on Pseudomonas aeruginosa infection.

The in vivo activity of human immunoglobulin M monoclonal antibody IN-2A8, which is specific for flagellum type b of Pseudomonas aeruginosa, was evaluated in comparison to anti-O antigen (serotype B) MAb KO-2F2 and in combination with antibiotics. IN-2A8 showed stronger activity than KO-2F2 against subcutaneous infection in burned mice, while it was much less active against intraperitoneal infection in normal mice. In a burn infection model, IN-2A8 inhibited the increase of bacteria in skin lesions weakly and that in blood significantly, suggesting that it strongly suppressed bacterial spread to blood. The activity of IN-2A8 in combination with 10 antipseudomonal antibiotics against intraperitoneal infection was examined. Clear additive effect was observed with a combination of either carbapenem or aminoglycoside antibiotics in terms of mouse survival. The administration of an antibiotic, imipenem-cilastatin, simultaneously with or before that of IN-2A8 gave a combined effect, but the reverse order did not. The combination of IN-2A8 with imipenem-cilastatin decreased numbers of viable bacteria in the peritoneal cavity and blood and kept them low for a longer time than did either treatment alone. These results suggest that an antiflagellar monoclonal antibody would be effective against systemic infection in combination with some kinds of antibiotics.

Animals↗

[Pathologic anatomy of Pseudomonas aeruginosa infections in children].

Examinations of 143 autopsy observations of P. aeruginosa infection in children were performed. Among them, 119 patients had pneumonia, 16 affections of the alimentary tract, 8 sepsis with various localizations of the primary focus. Morphologically the affected organs presented foci of necrosis of different size with tremendous numbers of bacteria, poor leukocyte reaction, and deep circulatory disorders in the periphery. A more manifest leukocyte infiltration in foci of lesions was observed in the cases where other bacterial microflora, in addition to P. aeruginosa, was present. P. aeruginosa isolated from the organs of dead children, as a rule, belonged to immune type 1 or 2 (according to Fisher's scheme). Microbiological studies on these strains showed the most marked necrotic changes to have been caused by microbes having such factors of pathogenicity as protease and plasmocoagulase.

Digestive System↗

Priming of neutrophils for enhanced oxidative burst by sputum from cystic fibrosis patients with Pseudomonas aeruginosa infection.

Neutrophils accumulate in the lungs of cystic fibrosis (CF) patients and inflict tissue damage by release of oxygen radicals and proteases. Here we report on the ability of sputum to prime neutrophils for enhanced release of oxygen radicals. Sol phase was prepared by ultracentrifugation of sputum obtained from CF patients attending the CF Clinic, Rigshospitalet, Copenhagen. The oxidative burst response of neutrophils from healthy individuals was measured by oxygen consumption, superoxide production and chemiluminescence. Neutrophils were preincubated with sputum or buffer and then stimulated with f-Met-Leu-Phe or zymosan. Appropriate controls were included in the experiments. It was shown that neutrophils preincubated with CF sol phase and stimulated with f-Met-Leu-Phe generated a three- to five-fold higher chemiluminescence response than those preincubated with buffer. There was no enhancement of the response when zymosan was used for stimulation of the cells. Neutrophils incubated with sol phase alone exhibited no response. Attempts were made to identify and partially characterize the priming factor(s). It was found that the sputum samples contained bacterial endotoxins. The priming activity was resistant to heating at 100 degrees C for 15 min, and was present only in fractions with molecules larger than 100 KD. It is suggested that the priming factor(s) consist of bacterial endotoxins and/or immune complexes. Activation and enhanced release of oxygen radicals from neutrophils may play an important role in the host defence as well as pathogenesis of tissue damage in the lungs of these patients.

Cystic Fibrosis↗