Pseudomonas aeruginosa

Infect Immun, 1989 Dec, 57(12), 3793 - 7
Pseudomonas aeruginosa elastase does not inactivate alpha 1-proteinase inhibitor in the presence of leukocyte elastase; Padrines M et al.; Pseudomonas aeruginosa elastase rapidly inactivates alpha 1-proteinase inhibitor by splitting its Pro-357-Met-358 peptide bond . The present study was aimed at testing whether this reaction takes place in the presence of leukocyte elastase . To this end was added alpha 1-proteinase inhibitor to a mixture of the two elastases, and we performed the following assays: (i) measurement of the residual leukocyte elastase activity, (ii) sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and (iii) immunoassay of the leukocyte elastase-alpha 1-proteinase inhibitor complex . These experiments were done with various concentrations of the three proteins . All experiments gave the same result: leukocyte elastase was fully inhibited by alpha 1-proteinase inhibitor in the presence of P . aeruginosa elastase even when the bacterial enzyme was 10-fold more concentrated than the neutrophil enzyme . We also measured the initial rate of the P . aeruginosa elastase-catalyzed inactivation of alpha 1-proteinase inhibitor as a function of the inhibitor concentration . The kcat/Km value derived from this experiment was 9 x 10(4) M-1 s-1, a value much lower than the rate constant for the leukocyte elastase-inhibitor association (kass, 1.7 x 10(7) M-1 s-1) . This rationalizes the above results . In conclusion, when alpha 1-proteinase inhibitor is faced with its target enzyme, leukocyte elastase, it will perform its physiologic antielastase function even if the bacterial elastase is present in excess.

Infect Immun, 1989 Dec, 57(12), 3783 - 7
Degradation of basement membranes by Pseudomonas aeruginosa elastase; Bejarano PA et al.; Pseudomonas aeruginosa virulence has been attributed in part to extracellular proteinases . We found that one of these proteinases, elastase, extensively degrades intact basement membranes from bovine anterior-lens capsules, bovine glomeruli, and bovine lung, producing about 9, 14, and 9 fragments, respectively, with Mrs in the range of 15,000 to greater than 200,000, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (nonreducing conditions) . Release of hydroxyproline showed that collagen IV was degraded by elastase . Degradation of the newly discovered alpha 3(IV) collagen chain was shown by immunoblotting of digests with Goodpasture's syndrome serum, which contains antibodies that react with an epitope located in the carboxyl-terminal globular (NCl) domain of alpha 3(IV) . Comparison of total protein release with collagen IV release showed that noncollagenous protein components were solubilized to the same extent as collagen IV . The extensive degradation of the basement membranes described here suggests a role for elastase in the pathogenic mechanism at the local level when P . aeruginosa infection is present.

Zh Mikrobiol Epidemiol Immunobiol, 1989 Dec, (12), 68 - 74
{Immunosuppression in experimental staphylococcal infection and its effect on antimicrobial resistance}; Barsukov VS; Experiments on CBA and (CBA X C57BL)F1 mice have revealed that a prolonged period of antigen-nonspecific immunosuppression of humoral immunity develops in experimental staphylococcal infection; this period of suppression may be preceded by a short phase of antigen-nonspecific immunostimulation . Immunosuppression is linked with the accumulation of antigen-nonspecific T-suppressors in the spleen, these T-suppressors being capable of the manifestation of their activity both in vitro and in vivo in cases of their transplantation to semi-syngeneic recipients . Immunosuppression does not aggravate the course of staphylococcal infection and is accompanied by an increase in resistance to Pseudomonas aeruginosa superinfection, which is due to the stimulation of inflammatory reaction at the site of the injection of the superinfecting agent.

APMIS, 1989 Dec, 97(12), 1146 - 8
Increased levels of IgG subclasses specific for Pseudomonas aeruginosa exoenzyme and polysaccharide antigens in chronically infected patients with cystic fibrosis; Albus A et al.; IgG subclass levels to Pseudomonas aeruginosa alginate, alkaline proteinase, elastase and exotoxin A in sera of healthy adults, non-infected and infected cystic fibrosis patients were investigated by enzyme linked immunosorbent assay . Whereas healthy adults and non-infected cystic fibrosis patients revealed mostly negative IgG subclass levels to the four antigens, infected cystic fibrosis patients had significantly elevated IgG1, IgG2, IgG3 and IgG4 levels to both the protein antigens as well as the polysaccharide antigen . The study does not support previous findings of an impaired natural IgG2 response to polysaccharide antigen . The study does not support previous findings of an impaired natural IgG2 response to polysaccharide in chronically infected cystic fibrosis patients.

Am J Med, 1989 Nov 30, 87(5A), 70S - 75S
Ciprofloxacin pharmacokinetics in critically ill trauma patients; Yuen GJ et al.; The steady-state pharmacokinetics of ciprofloxacin 200 mg intravenously every 12 hours was examined in 10 critically ill trauma patients . The mean parameter estimates for total clearance, renal clearance, non-renal clearance, and volume of distribution were 30.08 liters/hour/1.73 m2, 16.62 liters/hour/1.73 m2, 13.46 liters/hour/1.73 m2, and 2.10 liters/kg . Although the mean values were similar to those previously reported, significant individual differences were observed, with the coefficient of variation ranging from 41 to 61 percent . Non-renal clearance appeared to have a bimodal distribution . The dosage studied appeared to provide adequate serum concentration profiles to treat most pathogens found in infected trauma patients . However, the use of higher doses and more frequent dosing may be required to treat patients with Staphylococcus aureus and Pseudomonas aeruginosa infections.

Am J Med, 1989 Nov 30, 87(5A), 23S - 27S
Effect of the abscess environment on the antimicrobial activity of ciprofloxacin; Bryant RE et al.; The present studies were conducted to identify factors in human purulent material that might limit or enhance the activity of ciprofloxacin against bacteria causing suppurative infection . Ciprofloxacin, imipenem, and ampicillin were tested with regard to binding or inactivation by pus . The bactericidal activity of ciprofloxacin and imipenem were tested against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, or Staphylococcus aureus in human pus with a pH of 6.0 incubated at 37 degrees C under aerobic or anaerobic conditions . The effect of single or combination drug therapy with 20 mg/kg of ciprofloxacin, imipenem, or rifampin given every 12 hours was tested against E . coli or P . aeruginosa in polymicrobic murine abscesses that had been produced by subcutaneous injection of either of those organisms mixed with Bacteroides fragilis and autoclaved human stool . Antibiotic levels and the number of bacteria surviving in pus were quantitated . Therapy of subcutaneous abscesses was delayed 72 hours to test drug efficacy against organisms in well-established infections . Levels of ampicillin, imipenem, or ciprofloxacin were reduced from 10 micrograms/ml to 3.1 +/- 4.0, 2.7 +/- 3, or 5.8 +/- 2 micrograms/ml, respectively, after incubation in eight pus specimens for 24 hours at 37 degrees C . Ampicillin levels were reduced to less than 1 microgram/ml in four pus specimens containing beta-lactamase . Imipenem levels were undetectable in two specimens and were 0.2 micrograms/ml in one specimen . Ciprofloxacin binding to pus supernate or sediment appeared to be explained by its binding to the deoxyribonucleic acid (DNA) present in pus . Activity of 5 micrograms/ml of ciprofloxacin against four E . coli or K . pneumoniae strains in pus in vitro was greater than that of twofold higher concentrations of imipenem . The bactericidal activity of ciprofloxacin and imipenem were comparable but substantially reduced against S . aureus and P . aeruginosa in pus . Ciprofloxacin alone or regimens combining ciprofloxacin with rifampin or rifampin plus imipenem reduced the number of E . coli in polymicrobic subcutaneous abscesses but had little effect on P . aeruginosa in polymicrobic abscesses . The anaerobic abscess milieu appeared to inhibit the growth of P . aeruginosa . Ciprofloxacin activity in abscess fluid did not appear to be adversely affected by acid pH, aerobic or anaerobic conditions of incubation, the abscess constituents, or the binding of ciprofloxacin to the DNA in pus . Ciprofloxacin was bound to DNA of bacterial or human origin . Binding by pus was reversible, and binding to DNA extracts of pus was blocked by pretreatment of extracts with deoxyribonuclease but not by pretreatment with ribonuclease.(ABSTRACT TRUNCATED AT 400 WORDS)

Am J Med, 1989 Nov 30, 87(5A), 138S - 141S
Ciprofloxacin treatment of malignant external otitis; Sade J et al.; The Ear, Nose, and Throat department of the Meir Hospital treated 91 patients with malignant external otitis during the past 16 years . The last 23 patients with malignant external otitis were treated with ciprofloxacin 750 mg twice daily, combined with local excision of the aural lesion . The records of 61 of our previous 68 patients who underwent surgery and were hospitalized and treated with an intravenous extended-spectrum penicillin and gentamicin for six to eight weeks, were analyzed . Twenty-one of 23 patients treated with ciprofloxacin were cured; therapy failed in two patients . Treatment averaged 16.8 days of hospitalization, and bacteriologic eradication was achieved after an average of 7.04 days, as compared with 49 and 15.3 days, respectively, in the group of patients with the intravenous treatment . The mean peak concentrations of ciprofloxacin in serum varied between 2.5 and 3.7 micrograms/ml, and the drug concentrations in different ear tissues were 0.2 to 13 micrograms/g . The treatment with ciprofloxacin was well tolerated with no significant side effects, whereas serious side effects were noted in 45.9 percent of the previous intravenously treated group . The concentrations of the drug in serum and ear tissues were higher than the average minimal inhibitory concentration for Pseudomonas aeruginosa . Use of ciprofloxacin treatment, combined with local excision of the aural lesion, will bring about healing of malignant external otitis in the majority of cases . Ciprofloxacin can be given on an ambulatory basis after a relatively short period of hospitalization.

Am J Med, 1989 Nov 30, 87(5A), 123S - 127S
Use of ciprofloxacin in cystic fibrosis patients; Bosso JA; In order to evaluate the clinical efficacy and safety of oral ciprofloxacin in the treatment of acute pulmonary exacerbations of cystic fibrosis and trace the possible development of resistance over time, three trials were conducted . In an open-label, uncontrolled trial, 25 courses of ciprofloxacin were administered to 16 patients . Efficacy and safety were assessed based on changes in short-term clinical scores, white blood cell counts, Pseudomonas aeruginosa counts in sputum, pulmonary function tests, and standard serum chemistries and urinalysis that were performed before therapy, weekly during therapy, at the end of therapy, and at a seven-day follow-up visit after therapy . In an open-label, randomized, controlled study, the efficacy and tolerance of oral ciprofloxacin were compared with those of intravenous tobramycin and azlocillin . In another study, the rate of susceptibility of P . aeruginosa isolated from cystic fibrosis patients during more than two years of clinical use was determined . In the uncontrolled trial, ciprofloxacin therapy was associated with clinical improvement in most cases with changes in short-term clinical score and forced expiratory volume in one second being statistically significant (p less than 0.05) . Twenty-five patients were entered in the controlled trial with 12 patients in each treatment group being evaluable . The groups were comparable based on admitting demographic and disease characteristics, and no differences in therapeutic response or side effects were noted between the two treatments (p greater than 0.5) . Bacterial susceptibility to ciprofloxacin has remained relatively stable over time . Based on these results as well as those from similar evaluations, ciprofloxacin appears to be efficacious in the treatment of acute pulmonary exacerbations in adults with cystic fibrosis, producing responses similar to those observed with standard intravenous antibiotic therapy.

Am J Med, 1989 Nov 30, 87(5A), 28S - 31S
Resistance to ciprofloxacin appearing during therapy; Chin NX et al.; The development of resistance to ciprofloxacin in nine clinical isolates of Pseudomonas aeruginosa was investigated . Isolates had increases in minimal inhibitory concentrations (MICs) from 0.25 to 16 micrograms/ml . The isolates also became resistant to ofloxacin and norfloxacin, but did not show increases in MICs to aminoglycosides, antipseudomonas penicillins, or cephalosporins . One isolate from a patient with endocarditis showed a reduction in a 43-kD outer membrane protein and simultaneous increase in the imipenem MIC . This isolate also showed impaired uptake of ciprofloxacin . Respiratory isolates from cystic fibrosis patients did not show loss of outer membrane protein . MICs were lowered by ethylene diaminetetra-acetic acid, suggesting changes in lipopolysaccharide . Resistant isolates were synergistically inhibited by combinations of ciprofloxacin plus tobramycin or ceftazidime, but MICs remained beyond the achievable serum level.

Am J Med, 1989 Nov 30, 87(5A), 209S - 212S
Intravenous/oral ciprofloxacin therapy of infections caused by multiresistant bacteria; Neu HC et al.; Sixty patients were treated with ciprofloxacin: 19 received only intravenous ciprofloxacin, 41 received intravenous followed by oral ciprofloxacin . The mean duration of therapy was 28 days in the intravenous only group and 10 days intravenously and 80 days orally in the intravenous/oral group . Ten (17 percent) patients received 200 mg intravenously every 12 hours and 49 (82 percent) 300 mg every 12 hours . The overall clinical response was 85 percent, with a bacteriologic response of 70 percent . The lowest bacteriologic response (38 percent) occurred in the 13 patients treated for Pseudomonas respiratory infection . Clinical response occurred in 24 of 26 patients with soft-tissue infection, and 10 of 13 patients with respiratory infection . Of three patients with endocarditis, therapy failed in two with resistance developing in Pseudomonas aeruginosa and Staphylococcus aureus . Overall, 19 percent of 26 P . aeruginosa isolates developed resistance to ciprofloxacin . Toxicity was minor, with phlebitis and nausea most commonly reported . Intravenously administered ciprofloxacin or intravenous followed by oral ciprofloxacin is a safe, effective therapy for serious infections due to multiply resistant gram-negative bacteria, including P . aeruginosa and S . aureus.

S Afr Med J, 1989 Nov 18, 76(10), 543 - 5
The significance of Pseudomonas aeruginosa in chronic otitis media; Stolp DL et al.; Fifteen patients with chronic otitis media, where the organism cultured was Pseudomonas aeruginosa, had previously been treated with a variety of antibiotics, ear drops and surgical procedures . In 8 patients the discharge persisted . Between October 1986 and August 1987 these patients were treated with a combination of antibiotics (including piperacillin, ceftriaxone, amikacin and tobramycin) specific for Pseudomonas administered intravenously . In 7 patients the infection cleared completely . Follow-up ranged from 1 month to 1 year (average 4.5 months) . The regimen described could be of value in patients who do not respond to standard methods of treatment.

J Biol Chem, 1989 Nov 15, 264(32), 19022 - 7
Ligand binding to cytochrome c peroxidase from Pseudomonas aeruginosa; Greenwood C et al.; The high potential heme site of Pseudomonas cytochrome c peroxidase has His and Met as ligands . On reduction, the Fe-met bond becomes photosensitive . Following photolysis, the bond reforms with a half-time of 35 ps . The low potential heme peroxidatic site of the fully reduced enzyme has been shown to bind to a range of ligands . The compounds with carbon monoxide, methyl, ethyl, n-butyl, and t-butyl isonitriles have been investigated by laser flash photolysis . All are photosensitive and show different degrees of geminate recombination of ligand in the picosecond and nanosecond time ranges . Carbon monoxide shows the least effect . The three straight-chain isonitriles show about 50% geminate recombination with half-times of the order of 10 ns . t-Butyl isonitrile shows more and faster recombination . These results imply considerable freedom of movement within the active site for the smaller ligands.

J Biol Chem, 1989 Nov 15, 264(32), 18944 - 50
Difference in sodium requirement of branched chain amino acid carrier between Pseudomonas aeruginosa PAO and PML strains is due to substitution of an amino acid at position 292; Uratani Y et al.; Sodium dependence of leucine transport, a measure of the Na+-coupled leucine-isoleucine-valine II (LIV-II) transport system in Pseudomonas aeruginosa, was compared between two wild-type strains, PAO and PML . The leucine transport activity was saturated at 0.1 mM NaCl for PAO and at 5.0 mM for PML . From kinetics experiments, the apparent Km value for Na+ with respect to leucine transport was estimated to be 3 microM for PAO and 95 microM for PML . The Km value for leucine was 6 microM for PAO and 13 microM for PML . The LIV-II carrier gene (braB) of PML was isolated for comparison of its amino acid sequence with that of the PAO carrier cloned previously . The Km values for Na+ and leucine of the cloned LIV-II carriers of PAO and PML expressed in LIV-II defective mutants were similar to those in wild-type strains . Determination of the nucleotide and deduced amino acid sequences of the LIV-II carrier gene of PML showed an amino acid difference at position 292 between the PAO and PML carriers . The amino acid was threonine for PAO and alanine for PML . These results indicate that the substitution of the amino acid at position 292 of the LIV-II carrier causes a difference in the sodium requirement of the carriers of the PAO and PML strains.

Infect Immun, 1989 Nov, 57(11), 3549 - 54
Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD; Barbieri JT et al.; UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin . Incorporation of label from {3H-nicotinamide}NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from {32P-adenylate}NAD (0.2 mol/mol of protein) . Label from {3H-nicotinamide}NAD was specifically associated with Glu-129 . Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with {3H-nicotinamide}NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not . Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins . These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis.

J Foot Surg, 1989 Nov-Dec, 28(6), 542 - 6
Use of ceftazidime-impregnated polymethyl methacrylate beads in the treatment of Pseudomonas osteomyelitis; Tomczak RL et al.; Antibiotic-impregnated polymethyl methacrylate beads have been used in other countries to treat osteomyelitis . The drug of choice for this has historically been gentamicin . The authors have chosen ceftazidime to treat iatrogenic Pseudomonas aeruginosa osteomyelitis in rabbit femurs . After implanting the beads, the rabbits were killed at various times in the treatment period . Rabbits were killed at 15 days and later showed no signs of current osteomyelitis, including cultures and histologic examination . Blood antibiotic levels were measured at euthanasia and were minimal for all animals . It appears that ceftazidime may be an effective alternative to gentamicin, especially in treating gentamicin-resistant P . aeruginosa.

Arch Intern Med, 1989 Nov, 149(11), 2579 - 83
Oral ciprofloxacin vs parenteral cefotaxime in the treatment of difficult skin and skin structure infections . A multicenter trial; Gentry LO et al.; A prospective, randomized, double-blind, multicenter study was conducted of hospitalized patients to compare the efficacy and safety of oral ciprofloxacin (dosage, 750 mg every 12 hours) with intravenous cefotaxime (dosage, 2.0 g every 8 hours) as monotherapy for difficult skin and skin structure infections requiring hospitalization . Five hundred seventy patients were assessed for an analysis of safety and 461 patients were assessed for an analysis of efficacy . The most common infections were infected ulcers and abscesses . At the end of therapy, there was a higher incidence of recurrent or persistent organisms in the cefotaxime group compared with ciprofloxacin . Adverse reactions related to either therapy were rare . By pathogens, there were no differences in activity, except the higher rate of recurrent or persistent Pseudomonas aeruginosa infection in the cefotaxime group . By diagnosis, the two drugs had comparable efficacy, except for the higher incidence of bacteriologic failure in patients with polymicrobial infected ulcers in the cefotaxime group . Larger studies are needed to evaluate emergence of resistance to ciprofloxacin . Oral ciprofloxacin therapy is as safe and effective as parenteral cefotaxime in the treatment of difficult infections of the skin and skin structure, and affords the prospect of early discharge from the hospital and significant cost savings.

Infection, 1989 Nov-Dec, 17(6), 407 - 10
Adoptive transfer of resistance to Pseudomonas aeruginosa infection by splenocytes and bone marrow cells from BALB/c mice immunized by Pseudomonas aeruginosa lectin preparations; Avichezer D et al.; BALB/c mice immunized by intraperitoneal injection of purified Pseudomonas aeruginosa lectin preparations are fully protected against a lethal dose of the live bacteria . Intraperitoneal inoculation of splenocytes or bone marrow cells obtained from actively immunized mice into naive syngeneic mice was shown to significantly increase their resistance to P . aeruginosa infection . A similar transfer of splenocytes or bone marrow cells from untreated control mice did not provide protection against a lethal Pseudomonas challenge . Administration of immunocompetent cells from immunized animals to naive mice by the i.v . route was less efficient than the i.p . inoculation, probably due to different homing of the cells . Only the i.p . injection concentrated the immune cells to the site of infection.

Ther Drug Monit, 1989 Nov, 11(6), 692 - 5
The use of aerosolized tobramycin in the treatment of a resistant pseudomonal pneumonitis; McCall CY et al.; Aerosolized tobramycin was given to a 68-year-old man with resistant Pseudomonas aeruginosa pneumonitis at a dose of 100 mg every 8 h via a tracheostomy, after the patient failed to respond adequately to parenteral aminoglycoside and ticarcillin therapy . Minimum inhibitory concentration and minimum bactericidal concentration for tobramycin and gentamicin were 16 micrograms/ml and greater than 16 micrograms/ml, which necessitated aerosol administration . Tracheal concentrations 15 min and 4 h after a dose were 1,560 and 930 micrograms/ml . The patient responded and eventually was discharged from the hospital . Thus, monotherapy with an aerosolized aminoglycoside may be effective in some patients with resistant Pseudomonas aeruginosa pneumonitis.

J Hosp Infect, 1989 Nov, 14(4), 285 - 92
Two sources of contamination of a hydrotherapy pool by environmental organisms; Aspinall ST et al.; As a result of occasional water discolouration, the hydrotherapy pool of a large teaching hospital was monitored for free and combined chlorine, alkalinity, calcium hardness, total dissolved solids and cyanuric acid levels together with bacteriological analysis . The hose pipe supplying the pool and the dual water pumps were also examined as potential sources of bacterial contamination . The pool water yielded high counts of Pseudomonas vesicularis, Pseudomonas aeruginosa, and CDC Group IV C2, even in the presence of adequate levels of free chlorine . This was found to be due to high concentrations of cyanuric acid which resulted in a 'chlorine lock' . The source of the P . vesicularis and CDC Group IV C2 was found to be the pool hose and this problem was alleviated by flushing it with water each day before use . The source of the P . aeruginosa was the pool pumps, and was eradicated by regularly shock dosing them with 6-8 ppm of free chlorine.

J Clin Microbiol, 1989 Nov, 27(11), 2589 - 93
Use of a pilin gene probe to study molecular epidemiology of Pseudomonas aeruginosa; Speert DP et al.; Strains of Pseudomonas aeruginosa from patients with cystic fibrosis (CF) are unusual . The majority have a rough lipopolysaccharide (LPS) which renders them nontypeable by conventional typing systems based on a serological reaction with the O polysaccharide of smooth LPS . We developed a new typing scheme using a pilin gene probe as a marker for hybridization with endonuclease-digested genomic DNA from P . aeruginosa . Twenty-one different restriction fragment length polymorphism (RFLP) types were found among 249 isolates . RFLP type 7 was recovered only from patients with thermal burns (9 of 14 isolates) in both Vancouver, British Columbia, and Edmonton, Alberta, Canada . None of the other RFLP types showed a clear predilection for disease state or environmental niche . Multiple morphologically different isolates from individual patients with CF were studied; each isolate in 33 of 40 sputum samples had an identical RFLP type, despite considerable LPS serotype heterogeneity . Sequential isolates from 23 patients were studied; in 10 isolates there was a clear change in both the RFLP and the LPS serotype . We conclude that patients with CF usually harbor a single P . aeruginosa RFLP type in their sputa, but that one strain can replace another as the predominant colonizing type.

J Gen Microbiol, 1989 Nov, 135 ( Pt 11), 2819 - 27
Bacterial ethylene synthesis from 2-oxo-4-thiobutyric acid and from methionine; Mansouri S et al.; The ability of selected bacterial cultures to synthesize ethylene during growth in nutrient broth supplemented with methionine or 2-oxo-4-methylthiobutyric acid (KMBA) was examined . Although most cultures transformed KMBA into ethylene, only those of Escherichia coli SPAO and Chromobacterium violaceum were able to convert exogenously added methionine to ethylene . In chemically defined media, E . coli SPAO produced the highest amounts of ethylene from methionine and KMBA . This capability was affected by the nature of the carbon source and the type and amount of nitrogen source used for growth . When glutamate was used as sole source of carbon and nitrogen for growth, the activity of the ethylenogenic enzymes was reduced to 25% of that observed with cultures grown with glucose and NH4Cl . Neither methionine nor KMBA significantly affected the ethylenogenic capacity of E . coli SPAO . Menadione and paraquat, compounds that generate superoxide radicals, stimulated ethylene synthesis by harvested cells, but not by cell-free extracts of E . coli SPAO . In addition, cells of Pseudomonas aeruginosa, which produced no ethylene in culture in the presence of exogenously added KMBA, yet possessed the necessary enzymes in an active form, were able to synthesize ethylene from KMBA when incubated with menadione or paraquat.

J Antimicrob Chemother, 1989 Nov, 24(5), 731 - 40
Synergistic interaction of josamycin with human neutrophils bactericidal function in vitro; Labro MT et al.; Josamycin, a 16-membered ring macrolide is concentrated up to 20-fold in phagocytic cells compared with serum . We have studied the in-vitro interaction of this drug with human neutrophils (PMN) bactericidal function by using two strains resistant to this antibiotic, Pseudomonas aeruginosa and Klebsiella pneumoniae, and a sensitive one, Staphylococcus aureus 209P . It was shown that josamycin-pretreated adherent PMN displayed an increased phagocytic activity (about 30 to 40%) for S . aureus or K . pneumoniae, mainly due to the recruitment of an additional phagocytizing subset of PMN . Furthermore, the bacterial killing was enhanced in josamycin-treated PMN in a dose-dependent manner for K . pneumoniae (60-130% increase in the range of concentration 0.1-25 mg/l) and independently of the dose for S . aureus (about 425-460% increase for josamycin 0.1-10 mg/l) . P . aeruginosa killing by whole blood was also significantly increased in the presence of 10 and 1 mg/l of josamycin . Other PMN functions were not much altered by josamycin except an enhancement of the formyl-methionyl-leucyl-phenylalanine-induced oxidative response . Chemotaxis was only increased by the presence of a high concentration (100 mg/l) of josamycin . These data suggest that the bactericidal synergy between PMN and josamycin could be related, partly at least, to a direct enhancing effect of josamycin on some PMN functions such as phagocytosis, chemotaxis and FMLP-induced chemiluminescence . On the other hand, alterations of bacteria, either inside the phagolysosome or in the extracellular medium, could lead to an enhanced susceptibility to the phagocytes' microbial mechanisms.

Biochimie, 1989 Nov-Dec, 71(11-12), 1179 - 84
One-step affinity purification of amidase from mutant strains of Pseudomonas aeruginosa; Domingos A et al.; Amidases (acylamide amidohydrolase EC 3.5.1.4) from mutant strains (i.e., B6, AI3, AIU1N, OUCH 4 and L10) of Pseudomonas aeruginosa were purified in one-step by ligand affinity chromatography using Epoxy-activated Sepharose 4B-acetamide . The yields of the purified enzymes were about 90% for all mutant strains with purification factors of about 10 and were apparently homogeneous when analysed by SDS-PAGE and native PAGE . The protein bands on native PAGE coincided with the stained band of enzyme activity for all amidase preparations . Affinity columns had a maximum binding capacity of 0.5 mg amidase protein/ml of sedimented gel and could be regenerated and reused several times without any loss of binding capacity and resolution . Affinity gels containing either semicarbazide or urea were also found useful for the isolation of amidase . The differences in substrate specificity of these amidases reported previously were also observed in the elution behaviour of these enzymes from the affinity columns.

Appl Environ Microbiol, 1989 Nov, 55(11), 3016 - 9
Correlation of nitrogen metabolism with biosurfactant production by Pseudomonas aeruginosa; Mulligan CN et al.; A direct relationship between increased glutamine synthetase activity and enhanced biosurfactant production was found in Pseudomonas aeruginosa grown in nitrate and Proteose Peptone media . A chloramphenicol-tolerant strain showed a twofold increase in biosurfactant production and glutamine synthetase activity . Increased ammonium and glutamine concentrations repressed both phenomena.

Zh Mikrobiol Epidemiol Immunobiol, 1989 Nov, (11), 67 - 71
{The effect of staphylococci on the manifestation of opsonic cooperation in the complement system}; Konyshkina TM; The influence of the cultures of 14 Staphylococcus aureus and Staphylococcus epidermidis strains on the capacity of factor C3b of the complement for mediating the adhesive reaction of human neutrophils was studied . In experiments with 5 out of 11 S . aureus strains the essential weakening of reactions was registered, while one of the strains considerably enhanced reactions . Out of 3 S . epidermidis strains, the weakening of C3b-dependent reaction was noted in one case . The activity of the cultures did not correlate with the gelatinase properties of staphylococci and was absent in all gelatinase-positive Pseudomonas aeruginosa strains . The model worked out by the authors may be used for studying the influence of bacterial metabolites and biologically active substances on the effector properties of factor C3b of the complement.

Radiobiologiia, 1989 Nov-Dec, 29(6), 765 - 8
{Possibilities of using bacterial cultures for the biological indication of relatively small doses of gamma radiation}; Torosian MV et al.; Some approaches to using bacterial cultures as test objects in biological indication of relatively low gamma-radiation doses have been considered . The survival rate, mutability and induction of prophages in the lysogenic strains have been investigate . A model for the prophage induction in Pseudomonas aeruginosa is proposed to estimate the biological effect of gamma-irradiation with doses of 0.25 to 10 Gy.

Mol Microbiol, 1989 Nov, 3(11), 1493 - 9
Mapping the surface regions of Pseudomonas aeruginosa PAK pilin: the importance of the C-terminal region for adherence to human buccal epithelial cells; Lee KK et al.; The adherence of non-mucoid Pseudomonas aeruginosa strains is believed to be mediated by the pilus, which consists of a single protein subunit of 15,000 Daltons called pilin . Ten antipeptide antisera were raised to map the surface regions of pilin from P . aeruginosa strain K (PAK) . Only one of the antipeptide antisera to the eight predicted surface regions failed to react with PAK pili in direct ELISA . Five out of eight synthetic peptides representing the eight predicted surface regions reacted with anti-PAK pilus antiserum, indicating their surface exposure . Combining the antipeptide and antipilus antisera results, all eight predicted surface regions were demonstrated to be surface-exposed . The PAK 128-144-OH peptide produced the best binding antiserum to PAK pili . Only antipeptide Fab fragments directed against the disulphide bridged C-terminal region of PAK pilin blocked the adherence of pili to human buccal epithelial cells, which suggests that this region contains the receptor-binding domain of the PAK pilus.

J Gen Microbiol, 1989 Nov, 135 ( Pt 11), 3023 - 34
Early cell envelope alterations by tobramycin associated with its lethal action on Pseudomonas aeruginosa; Raulston JE et al.; The immediate activities of the aminoglycoside antibiotic tobramycin were investigated in Pseudomonas aeruginosa PAO1 . The lethal action of a low concentration of tobramycin (8 micrograms ml-1) occurred rapidly (1-3 min) and was associated with leakage of certain cellular components into the supernatant . The presence of magnesium at the time of initial exposure protected cells by preventing uptake of tobramycin; however, magnesium addition following a brief exposure did not restore viability . Analyses of supernatant material revealed a rapid 2-fold increase in protein released following tobramycin treatment . A prominent 29 kDa protein, observed by SDS-PAGE in the released material was identified as the periplasmic beta-lactamase . Brief exposure to tobramycin did not result in major morphological damage or cell lysis as observed by transmission electron microscopy, and release of LPS was not a primary event . Although activity at the ribosomal level was observed by 2-3 min, leakage was detected after only 1 min . These data indicate that leakage of cellular components, particularly beta-lactamase, occurs simultaneously, if not prior to inhibition of protein synthesis by tobramycin.

Curr Eye Res, 1989 Nov, 8(11), 1163 - 9
Tobramycin iontophoresis into corneas infected with drug-resistant Pseudomonas aeruginosa; Hobden JA et al.; Iontophoretic application of tobramycin was used to deliver drug to the cornea of rabbit eyes infected with a tobramycin-resistant strain of Pseudomonas aeruginosa (MIC = 31.25 micrograms/ml) . Corneas infected with P . aeruginosa 27853/pMG6 were treated 22 hours after infection with tobramycin delivered by either iontophoresis, mock iontophoresis (eye cup without current), or application of fortified topical drops . Corneal iontophoresis of tobramycin at 25 mg/ml caused more than a three log reduction in bacteria; yielding a significantly lower number of bacteria compared to untreated controls and all other treatments (P less than or equal to 0.0001) . Corneal iontophoresis of tobramycin at 10 mg/ml showed a one log reduction in the number of bacteria per cornea, yielding a significantly lower number of bacteria compared to untreated controls (P less than or equal to 0.0001), corneas treated with nine topical applications of 1.36% tobramycin drops (P less than or equal to 0.0001), and corneas treated with mock iontophoresis (P less than or equal to 0.02) . These results suggest that iontophoresis is a powerful ocular delivery system for tobramycin and may be suitable for use with other chemotherapeutic agents.

Antimicrob Agents Chemother, 1989 Nov, 33(11), 1936 - 8
Phosphanilic acid inhibits dihydropteroate synthase; Eagon RG et al.; Intact cells of Pseudomonas aeruginosa were more susceptible to phosphanilic acid (PA) than cells of Escherichia coli . In cell extracts, the dihydropteroate synthases of P . aeruginosa and E . coli were about equally susceptible to inhibition by PA . These results suggest that cells of P . aeruginosa are more permeable to PA than cells of E . coli . Although a weak inhibitor, PA acted on dihydropteroate synthase in the same manner as the sulfonamides with which PA is structurally related . Inhibition of E . coli by PA in a basal salts-glucose medium was prevented by p-aminobenzoic acid (pABA) . However, pABA did not protect P . aeruginosa from PA under these conditions, possibly because pABA itself exhibited an inhibitory effect . PA also appeared to have a second mode of action . The mechanism was not elucidated.

Antimicrob Agents Chemother, 1989 Nov, 33(11), 1921 - 6
Factors influencing the accumulation of ciprofloxacin in Pseudomonas aeruginosa; Celesk RA et al.; Ciprofloxacin accumulation in Pseudomonas aeruginosa was measured by a bioassay . Drug accumulation in strain PAO2 was compared with that of three spontaneous ciprofloxacin-resistant mutants selected with 0.5 micrograms of ciprofloxacin per ml . PAO4701 cfxA2 contains a mutation in the gyrA gene, PAO4742 cfxB5 may represent a permeability mutant based on pleiotropic drug resistance, and PAO4700 cfxA1 cfxB1 contains both types of mutations . In all strains, drug accumulation was similar, reaching steady state during the first minute of exposure . Drug accumulation was unsaturable over a range of 5 to 80 micrograms/ml, suggesting that ciprofloxacin accumulates by diffusion in P . aeruginosa . Although all four strains accumulated two- to sevenfold more ciprofloxacin in the presence of the inhibitor carbonyl cyanide m-chlorophenylhydrazone, the cfxB mutants accumulated two- to fourfold less drug than either PAO2 or the cfxA2 mutant . Polyacrylamide gel analysis revealed a protein common to cfxB mutants only, while all strains had similar lipopolysaccharide profiles . The results suggest that ciprofloxacin accumulation in P . aeruginosa is a complex phenomenon that may be affected by both an energy-dependent drug efflux process and outer envelope composition.

Arch Dis Child, 1989 Nov, 64(11), 1599 - 603
Pseudomonas aeruginosa antibodies in blood spots from patients with cystic fibrosis; Thanasekaraan V et al.; The formation of antibodies to Pseudomonas aeruginosa may be the earliest indicator of pulmonary infection in patients with cystic fibrosis . To enable easy sampling in babies and young children an enzyme linked immunosorbent assay (ELISA) based on a blood spot sample taken on to blotting paper was developed . A sample of approximately 20 microliters of blood was required . A high correlation and level of absolute agreement was shown between paired finger prick and venepuncture blood spots, and between blood spot, serum spot, and serum samples . Healthy controls and non-infected patients with cystic fibrosis had low titres of antibody compared with patients with intermittent and chronic infection . The latter groups had significantly greater antibody titres than normal controls . This assay permits serial measurement of antibodies to P aeruginosa in patients of all ages with cystic fibrosis and may provide a means of assessing the value of such measurements in the detection and management of early infection.

Circ Shock, 1989 Nov, 29(3), 245 - 56
Cardiopulmonary changes occurring with pulmonary intravascular clearance of live bacteria in sheep; Dehring DJ et al.; Sheep were infused with live bacteria to determine if the bacteria are phagocytized in the pulmonary circulation and to study the associated cardiopulmonary changes . Unanesthetized animals (n = 9) with chronic hemodynamic and pulmonary lymph catheters received a 1 hr central venous infusion of live Pseudomonas aeruginosa (5 x 10(7) Ps./minute) and were compared to a sham group (n = 7) . The pulmonary arterial levels of bacteria were five to 100 times higher than the aortic levels . Pulmonary intravascular clearance rates were 79-91% . Electron microscopy of the lungs 24 hr after the bacterial infusion showed that pulmonary intravascular macrophages and neutrophils phagocytosed the bacteria . Severe initial and mild persistent pulmonary hypertension occurred . The pulmonary lymph flow was elevated, initially from hydrostatic pressure and later from increased permeability . A hyperdynamic circulation occurred from 6 to 18 hr, with elevated cardiac index and lowered systemic vascular resistance and mean arterial pressure, mimicking cardiopulmonary changes seen in clinical sepsis . The removal of bacteria in the lungs may contribute to the injury in sheep.

Arch Ophthalmol, 1989 Nov, 107(11), 1667 - 70
Effect of lid closure on contact lens-associated Pseudomonas keratitis; Aswad MI et al.; New or used extended-wear soft contact lenses, preincubated in suspensions of Pseudomonas aeruginosa, were placed on the corneas of rabbits . The lids were then sutured shut for either 1 or 2 weeks . Bacterial keratitis occurred in 9 of 9 eyes fitted with the used contaminated lenses but in none of 12 eyes fitted with new contaminated or new noncontaminated lenses . Similar experiments were carried out with other lenses specifically designed to fit the cornea of rabbits . Some of these lenses were preworn by rabbits for 1 week (used), whereas others were new . A significantly greater incidence of bacterial keratitis was found in eyes that had undergone lid closure after the placement of used contaminated lenses (4 of 5) than in closed eyes with new contaminated lenses (1 of 8) and in open eyes with used contaminated lenses (0 of 13) . These findings suggest that extended eyelid closure is a risk factor in the experimental model and may be a factor in clinical Pseudomonas keratitis associated with the wearing of extended-wear soft contact lenses.

J Clin Microbiol, 1989 Nov, 27(11), 2616 - 8
Pseudomonas aeruginosa ATCC 49189, a new quality control strain for testing P . aeruginosa susceptibility to the aminoglycosides; Lally RT et al.; Quality control for in vitro antimicrobial susceptibility testing of Pseudomonas aeruginosa versus aminoglycosides is improved by P . aeruginosa ATCC 49189, which was developed in the Clinical Microbiology Laboratory at St . Paul-Ramsey Medical Center . This strain, used by us for daily testing for the past 6 years, requires MICs that approximate therapeutic concentrations, are midrange in most dilution schemes, and are stable and reproducible.

J Bacteriol, 1989 Nov, 171(11), 6357 - 62
Cloning and expression of Pseudomonas aeruginosa flagellin in Escherichia coli; Kelly-Wintenberg K et al.; The flagellin gene was isolated from a Pseudomonas aeruginosa PAO1 genomic bank by conjugation into a PA103 Fla- strain . Flagellin DNA was transferred from motile recipient PA103 Fla+ cells by transformation into Escherichia coli . We show that transformed E . coli expresses flagellin protein . Export of flagellin to the E . coli cell surface was suggested by positive colony blots of unlysed cells and by isolation of flagellin protein from E . coli supernatants.

J Bacteriol, 1989 Nov, 171(11), 6300 - 6
Cloning and nucleotide sequence of braC, the structural gene for the leucine-, isoleucine-, and valine-binding protein of Pseudomonas aeruginosa PAO; Hoshino T et al.; The gene for the leucine-, isoleucine-, and valine-binding protein (LIVAT-BP) in Pseudomonas aeruginosa PAO was isolated, and its nucleotide sequence was determined . The gene consisted of 1,119 nucleotides specifying a protein of 373 amino acid residues . Determination of the N-terminal amino acid sequence of the LIVAT-BP purified from P . aeruginosa shock fluid suggested that the N-terminal 26 residues of the gene product are cleaved off posttranslationally, showing the characteristic features of procaryotic signal peptides . The amino acid composition of the mature product predicted from the nucleotide sequence was in good agreement with that of the purified LIVAT-BP . The plasmid carrying the LIVAT-BP gene restored the activity of the high-affinity branched-chain amino acid transport system (the leucine, isoleucine, valine {LIV-I} transport system) in the braC310 mutant of P . aeruginosa, confirming that braC is the structural gene for LIVAT-BP . The mutant LIVAT-BP lacking a 16-amino-acid peptide in the middle was found to be functional in the LIV-I transport system . LIVAT-BP showed extensive homology (51% identical) to the LIV- and leucine-specific-binding proteins of Escherichia coli K-12, which are coded for by the livJ and livK genes, respectively, suggesting that the role of the proteins in the LIV-I transport systems is analogous in both organisms.

Infect Immun, 1989 Nov, 57(11), 3491 - 7
Evidence for different pyoverdine-mediated iron uptake systems among Pseudomonas aeruginosa strains; Cornelis P et al.; Fourteen strains of Pseudomonas aeruginosa (P . aeruginosa ATCC 15692, P . aeruginosa ATCC 27853, and 12 clinical isolates) were checked for the production of pyoverdine and for pyoverdine-mediated iron uptake . Under iron restriction, two isolates produced undetectable amounts of pyoverdine, but all the other strains produced a compound with physicochemical properties identical or close to those of the pyoverdine of P . aeruginosa ATCC 15692 (strain PAO1) . The pyoverdines were purified and tested for their growth-promoting activity and for their ability to facilitate 59Fe uptake in homologous experiments involving each pyoverdine and its producing strain, as well as in heterologous systems involving all the other strains . The results of both types of experiments suggested the existence of three specificity groups . This was confirmed by analysis of the amino acid composition of the pyoverdines, which differed for each group . A partially purified polyclonal antiserum raised against a major 80-kilodalton (kDa) iron-regulated outer membrane protein (IROMP) of P . aeruginosa PAO1 recognized the 80-kDa IROMPs from P . aeruginosa PAO1 and the clinical isolates belonging to the same group, whereas the IROMPs from the strains belonging to the two other groups were not detected . A second antiserum raised against the P . aeruginosa ATCC 27853 80-kDa IROMP gave similar results by reacting specifically with the 80-kDa IROMP from the strains belonging to this group . Thus, together with the already known pyoverdine from P . aeruginosa PAO1, two new types of pyoverdines produced by strains belonging to this species were characterized.

Carbohydr Res, 1989 Oct 31, 193, 75 - 90
Synthesis of a common polysaccharide antigen of Pseudomonas aeruginosa as the 6-aminohexyl glycoside; Tsvetkov YE et al.; The synthesis is described of a tritylated 1,2-O-cyanoethylidene derivative (3) of the trisaccharide alpha-D-Rha-(1----2)-alpha-D-Rha-(1----3)-D-Rha . Triphenylmethylium perchlorate-catalysed polycondensation of 3 in the presence of 6-phthalimidohexyl 2,4-di-O-benzoyl-3-O-trityl-alpha-D-rhamnopyranoside followed by deprotection afforded the 6-aminohexyl glycoside of a D-rhamnan corresponding to a common polysaccharide antigen of Pseudomonas aeruginosa.

Biochem Biophys Res Commun, 1989 Oct 31, 164(2), 601 - 8
Control of alginate synthesis in Pseudomonas aeruginosa: regulation of the algR1 gene; Kimbara K et al.; The triggering of mucoidy (formation of the exopolysaccharide alginate) in Pseudomonas aeruginosa is accomplished primarily in Cystic Fibrosis lung environment through activation of the promoter of a gene algD, which encodes GDP-mannose dehydrogenase, by the product of a regulatory gene algR1 . Both algD and algR1 promoter regions have significant homology, including the presence of sequences recognized by the RNA polymerase sigma 54 . We demonstrate that the algR1 promoter is partly constitutive and its activation, similar to that of algD, is dependent on high osmolarity as well as the presence of its own gene product and is repressed by high concentrations of AlgR1 . The RpoN sigma factor also plays a critical role in the transcription of both algD and algR1 genes.

J Immunol, 1989 Oct 15, 143(8), 2609 - 16
Bactericidal defect of neutrophils in a guinea pig model of thermal injury is related to elevation of intracellular cyclic-3',5'-adenosine monophosphate; Bjornson AB et al.; PG of the E series inhibit major effector functions of polymorphonuclear leukocytes (PMN) by elevating intracellular cAMP . The present study investigated the involvement of this mechanism in the bactericidal defect of PMN induced by thermal injury in a guinea pig model . Peripheral and peritoneal exudate PMN harvested from thermally injured guinea pigs at 1 or 2 days postburn had decreased bactericidal activity against Pseudomonas aeruginosa and a marked increase in cAMP content . Production of PGE1 by these cells in the absence of exogenous PMN activators was also increased . Treatment of PMN in vitro or in vivo with nonsteroidal anti-inflammatory drugs (indomethacin, ibuprofen, and piroxicam) restored bactericidal activity to normal and concomitantly reduced cAMP content and PGE1 production . A concomitant reduction in cAMP content and PGE1 production was also observed as bactericidal activity of PMN returned to normal under natural conditions during 4 to 7 days postburn . The enhancement of PMN bactericidal activity mediated by NSAID was fully counteracted by purified PGE1, theophylline, and by cAMP itself . These results suggest that the bactericidal defect of PMN induced by thermal injury is related to elevation of cAMP and that PGE1 plays a significant role in this phenomenon.

Pol Tyg Lek, 1989 Oct 23-Nov 6, 44(43-45), 924 - 7
{Results of using polyvalent Pseudomonas aeruginosa vaccine in children with burns by various medical centers}; Bbukowska D et al.; Polyvalent Pseudomonas aeruginosa vaccine, prepared at the Institute of Hematology from 10 hospital strains isolated from burn wounds, was administered to 32 children with extensive and deep burns . The vaccine was well tolerated . The vaccine produced a high degree of the immunity against Pseudomonas aeruginosa infection . Agglutinin serum titre increased significantly . Vaccination either prevented or inhibited the infection of burn wounds with Pseudomonas aeruginosa in all immunized children . The symptoms of Pseudomonas aeruginosa infection usually disappeared following one or two vaccinations . Bacteriemia caused by P . aeruginosa was not observed in 31 out of 32 children . In the remaining child transient bacteriemia was noted . No septicemia caused by P . aeruginosa was seen . Due to the high efficiency of the polyvalent P . aeruginosa vaccine all burned children with burns exceeding 10% of the total body surface should by vaccinated to prevent the life-threatening infections with Pseudomonas aeruginosa.

Infect Immun, 1989 Oct, 57(10), 3066 - 71
Differences in adhesion of Pseudomonas aeruginosa to mucin glycopeptides from sputa of patients with cystic fibrosis and chronic bronchitis; Ramphal R et al.; Pseudomonas aeruginosa is the most prominent colonizer of the respiratory tract of patients with cystic fibrosis, but it is not known why this occurs . P . aeruginosa adheres to mucins from normal individuals, but mucins from cystic fibrosis patients have not been studied . To compare adhesion to mucins from cystic fibrosis with other mucins, we prepared highly glycosylated mucin glycopeptides from cystic fibrosis and chronic bronchitis patients by ion-exchange and gel-filtration chromatography and measured the adhesion of P . aeruginosa 1244 to these glycopeptides . We found (i) that the most mucinlike glycopeptides from P . aeruginosa-infected cystic fibrosis sputa showed less bacterial adhesion than did the corresponding bronchitis samples, (ii) that the most adhesive activity in cystic fibrosis samples came from a fraction that contains O and N glycopeptides and may be in part a degradation product of P . aeruginosa infection, and (iii) that highly glycosylated glycopeptides of the most acidic species (sialylated and sulfated) showed no adhesion at all . A single cystic fibrosis sample not infected by P . aeruginosa showed better binding in the adhesion-positive fractions than did the infected sputa . These studies suggest that cystic fibrosis mucins may be altered after infection is established, resulting in less binding to some fragments . However, since the clinical picture shows heavy mucus colonization, other receptors, such as cellular glycolipids which have been shed into mucus, may be contributing to this colonization.

J Antimicrob Chemother, 1989 Oct, 24(4), 591 - 604
Prospective comparative trial of short course (four day) and continuous tobramycin in combination with cefoperazone or mezlocillin in febrile, granulocytopenic patients; Pegram PS et al.; In a prospective, randomized trial of 195 febrile episodes in granulocytopenic patients short course aminoglycoside treatment (initial tobramycin and cefoperazone followed by tobramycin discontinuation at day four of therapy) was compared with two regimens (tobramycin plus cefoperazone and tobramycin plus mezlocillin) in which both drugs were continued for up to 26 days . All regimens were successful as empirical therapy with comparable response rates of just over seventy per cent . Fifty-three per cent of the initial episodes of fever were related to documented infections which responded less well (P = 0.007) than unexplained fever . Patients with bacteraemia, pneumonia or Gram-positive aerobic or Pseudomonas aeruginosa infections responded poorly to all regimens . The recovery from granulocytopenia was the most important determinant of successful response . Aminoglycoside discontinuation followed by cefoperazone monotherapy after day four was statistically as effective as the combination regimens . Short course tobramycin therapy eliminated the nephrotoxicity seen in the combination limbs . The use of cefoperazone was not associated with an increased incidence of hypoprothrombinemia; however, the only three bleeding episodes occurred in patients given cefoperazone but not vitamin K . Short course aminoglycoside therapy will reduce cost and nephrotoxicity when compared with prolonged combination therapy and should be further explored in this setting, with use of different agents and comparison with monotherapy.

Rev Ig Bacteriol Virusol Parazitol Epidemiol Pneumoftiziol Bacteriol Virusol Parazitol Epidemiol, 1989 Oct-Dec, 34(4), 325 - 36
{A nonspecific immunostimulant effect with Cantastim on the cellular and humoral immune responses in mice evaluated by in vivo and in vitro tests}; Olinescu A et al.; The stimulatory effect was evaluated, of an ethanol extraction obtained from a pathogenic strain of Pseudomonas aeruginosa type XV . It was noted that this extract, commercially known as "Cantastim" has mitogenic effects in vitro for mouse lymphocytes, but not for those of humans or of guinea pigs . It activates the cytostatic functions of macrophages . It is thermoresistant, nonimmunogenic and it is not allergic . A low amount of proteins and carbohydrates are contained in this extract, but it contains over 80% phospholipids . It has a transient stimulating effect of the cytotoxic effects of NK cells, and it also activates the synthesis of antibodies from the IgM and the IgG classes . It probably stimulates the expression of receptors for PHA in the membrane of T lymphocytes, and retards the development of the Ehrlich ascites tumour, protecting at the same time the animals from severe infections with conditionally pathogenic germs . These data suggests that "Cantastim" is a potent immunomodulating agent that could be used successfully in the fight against certain chronic diseases with a bacterial or neoplastic etiology of humans.

J Infect Dis, 1989 Oct, 160(4), 657 - 61
Pseudomonas osteochondritis complicating puncture wounds of the foot in children: a 10-year evaluation; Jacobs RF et al.; From 1978 to 1988, microbiologically proven Pseudomonas osteochondritis and septic arthritis following nail puncture wound to the foot was diagnosed in 77 children aged 18 mo-19 y (77 and 17 cases, respectively) . The syndromes were found in children with a history of wearing tennis shoes (70 cases), other shoes (5), and no shoes (2) . All cases had surgical debridement of the infected cartilage or bone and drainage of infected joints . Pseudomonas aeruginosa was isolated in 38 cases and in conjunction with Staphylococcus aureus in 18 . Anti-Pseudomonas antibiotics were initiated in all cases before surgical exploration; the average duration of treatment was 7.5 +/- 1.2 d postoperatively . Patient follow-up was 5.2 +/- 3.4 y (median, 4.8 y; range, 3 mo-10 y) . Two relapses occurred; both patients had a previously undetected septic arthritis . These data suggest that with aggressive surgical management, Pseudomonas osteochondritis and septic arthritis can be treated effectively with postoperative antibiotics for 7 d.

Jpn J Exp Med, 1989 Oct, 59(5), 189 - 96
Thermal injury-induced non-specific resistance to fatal Pseudomonas aeruginosa burn-infection in mice; Pinto M et al.; Nonlethal thermal injury in mice results in rapid death by immediate injection of 10(3) viable P . aeruginosa in the skin of the burn sites . Resistance to the lethal burn combined with P . aeruginosa infection developed 24 h after initial thermal injury and reached maximal effect 7 days later; it then continued for at least 21 days . The optimal survival was achieved when the first thermal injury was made for 7 seconds at 350 degrees C . Increased resistance, but for a short period could also be obtained by injection of lipopolysaccharide (LPS) 1-4 days prior to the burn-P . aeruginosa infection . However, when the LPS was injected immediately after the burn-infection, the lethal effect was increased . The induction of late protection after thermal injury and bacterial infection was demonstrated with P . aeruginosa organisms only . Under similar schedule of thermal injury resistance was not induced by infection with Semliki forest virus . On the contrary viral infection increased the susceptibility of burned mice to a fatal outcome . Immune or natural antibodies were not elevated in the sera of post burn mice . Furthermore, delayed type hypersensitivity response, as evaluated by a footpad weight assay was inhibited and this inhibition persisted at least for 7 days post burn . The thymus weight and its lymphoid cell content in thermally injured mice decreased significantly 7 days post burn, whereas the weight of the spleen increased and it contained fewer lymphocytes per gram tissue . We suggest that endotoxin entering the systemic circulation post-burn might be one of the factors contributing to the early sensitivity and the late protection against the fatal P . aeruginosa burn-infection.

Antimicrob Agents Chemother, 1989 Oct, 33(10), 1724 - 8
Fatty acid alterations and polymyxin B binding by lipopolysaccharides from Pseudomonas aeruginosa adapted to polymyxin B resistance; Conrad RS et al.; Lipopolysaccharides were extracted from freeze-dried cells of Pseudomonas aeruginosa PAO1 (polymyxin B susceptible), isolate A (polymyxin B resistant), and isolate A-reverted (polymyxin B intermediate resistance) by either the phenol-chloroform-petroleum ether or the modified phenol-water method . Isolate A and isolate A-reverted had drastic losses of 2-hydroxydodecanoic acid and significant decreases in 3-hydroxydecanoic acid . Concentrations of amide-linked 3-hydroxydecanoic acid were similar in all three strains . Minor alterations were noted in the composition of 3-deoxy-D-manno-2-octulosonic acid, heptose, phosphate, neutral sugars, and amino compounds . The concentrations of rhamnose in isolate A and of rhamnose and glucose in isolate A-reverted were significantly different from those in PAO1 . Trace amounts of mannose and other minor unidentified carbohydrates were detected in all strains . Polymyxin B included in isolate . A growth medium complexed with lipopolysaccharides and remained bound throughout purification . PAO1 lipopolysaccharides bound more polymyxin B than did isolate A lipopolysaccharides . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated minor differences in smooth- and rough-form lipopolysaccharides of the different strains . We propose that loss of hydroxy fatty acids from lipopolysaccharides perturbs outer membrane hydrophobicity and is a contributing factor to polymyxin B adaptive resistance.

Wei Sheng Wu Xue Bao, 1989 Oct, 29(5), 378 - 82
{Studies on the adherent factors of Pseudomonas aeruginosa with bioluminescence}; Sun JY et al.; A bioluminescence method was established for quantifying the adhesion of P . aeruginosa to polystyrene and the adherent components were investigated . The results indicated that the slime polysaccharide (SPS) is an important adherent factor of some slime strains of P . aeruginosa . The adhered amount of washed slime strains could be increased by pre-coating of polystyrene with SPS obtained from PA3 . The activity of PA3SPS could be inhibited by anti-PA3SPS antiserum and blocked by N-acetylglucosamine.

Wiad Lek, 1989 Oct 1-Nov 1, 42(19-21), 1028 - 32
{Sensitivity to antibiotics of Pseudomonas aeruginosa isolated from patients in the years 1986-1988}; Gosciniak G et al.; Pseudomonas aeruginosa strains (240 in all) isolated from various clinical materials in the years 1986-1988 showed a high sensitivity to amikacin (92.3-100%), colistin (84.6-100%) and ceftazidim (84.6-100%) . Netilmycin acted on 75.4% of the strains, and penicillins (carbenicillin, ticarcillin and azlocillin) similarly as gentamicin, tobramycin, cefotaxim, cefoperazon and ceftriaxon were active only against 51.3-66.7% of the tested strains.

FEMS Microbiol Lett, 1989 Oct 1, 52(1-2), 33 - 6
Outer membrane proteins of gentamicin induced small colony variants of Pseudomonas aeruginosa; Langford PR et al.; Small colony variants (SCVs) of Pseudomonas aeruginosa NCTC 6750 (WT) were repeatedly isolated in an in vitro kinetic model after exposure to gentamicin (GM) . There were minor differences biochemically and in phage and serotyping between the wild type (WT) strain and SCVs . Changes in outer membrane protein profiles were found . SCVs were more resistant to polymixin and to a range of aminoglycosides (except kanamycin), but were more susceptible to a range of other antibiotics (hydrophilic and hydrophobic) with differing modes of action.

Eur J Clin Microbiol Infect Dis, 1989 Oct, 8(10), 917 - 9
Comparative in vitro activity of cefepime (BMY 28142) against multiresistant nosocomial isolates of Pseudomonas aeruginosa; Voutsinas D et al.; The in vitro activity of a new parenteral cephalosporin cefepime (BMY 28142) was compared with that of ceftazidime, cefotaxime, piperacillin, imipenem, gentamicin, amikacin and ciprofloxacin against 173 recent multiresistant Pseudomonas aeruginosa isolates of nosocomial origin using an agar dilution technique with an inoculum of 10(4) CFU per spot . The activity of cefepime was comparable to that of ceftazidime, superior to that of cefotaxime, piperacillin, gentamicin and amikacin, but inferior to that of imipenem and ciprofloxacin . Cross-resistance of Pseudomonas aeruginosa to ceftazidime and cefepime occurred in nearly 50% of the cefepime resistant strains and 61.5% of the ceftazidime resistant strains respectively.

Eur J Clin Microbiol Infect Dis, 1989 Oct, 8(10), 858 - 65
Antipseudomonal therapy in cystic fibrosis: aztreonam and amikacin versus ceftazidime and amikacin administered intravenously followed by oral ciprofloxacin; Schaad UB et al.; In order to determine the optimal antipseudomonal therapy in patients with cystic fibrosis aztreonam plus amikacin was compared to ceftazidime plus amikacin, and these two-week hospital regimens were followed by oral ciprofloxacin given for four weeks . Fifty-six cases of acute pulmonary exacerbation of the disease in 42 patients associated with isolation of Pseudomonas aeruginosa from the sputum were randomly treated with either aztreonam or ceftazidime (300mg/kg/day i.v.; maximum daily dose 12g) in combination with amikacin (36mg/kg/day i.v.; maximum daily dose 1,500mg) . Other aspects of the two-week treatment were constant . The two therapy groups were comparable in all respects . Both regimens were well tolerated and resulted in similar improvements in clinical, bacteriologic, radiologic and laboratory findings, and pulmonary function . Fifty patients could be reevaluated after subsequent outpatient therapy consisting of oral ciprofloxacin (30mg/kg/day; maximum daily dose 1,500mg) given for four weeks . During this period, the clinical and laboratory improvements persisted, and the rate of eradication of Pseudomonas aeruginosa from sputum decreased from 62% to 34% . Ciprofloxacin was well tolerated and there was no drug toxicity or serious adverse effect . In the 25 prepubertal patients there was neither subjective nor objective evidence of skeletal drug toxicity . In patients with cystic fibrosis, aztreonam or ceftazidime in combination with amikacin represents an effective and safe systemic anti-pseudomonal therapy . Subsequent oral ciprofloxacin therapy for four weeks prolongs the beneficial effects and is well tolerated.

Antimicrob Agents Chemother, 1989 Oct, 33(10), 1741 - 7
Sodium hexametaphosphate sensitizes Pseudomonas aeruginosa, several other species of Pseudomonas, and Escherichia coli to hydrophobic drugs; Vaara M et al.; Many gram-negative bacteria are known to be remarkably resistant to hydrophobic noxious agents by virtue of their outer membranes (OM) . We investigated, by using four different assay methods, the ability of sodium hexametaphosphate (HMP) to disrupt this OM barrier . (i) In the growth inhibition assay, HMP was found to sensitize strains of Pseudomonas aeruginosa to all the hydrophobic probes tested (rifampin, fusidic acid, dactinomycin, sodium dodecyl sulfate, and Triton X-100) . A concentration of 0.3% HMP decreased the MICs of the probes by a factor of approximately 10, and maximally even a 30-fold sensitization was found with 1% HMP . (ii) In the bactericidal assay, 0.3% HMP decreased the MBC of the hydrophobic probe rifampin by a factor of approximately 30 . (iii) In the bacteriolytic assay, 0.1% HMP sensitized the target bacteria to lysis by sodium dodecyl sulfate and Triton X-100 . (iv) In the fluorescent-probe binding assay, HMP drastically enhanced the binding of fluorescent N-phenyl naphthylamine to the membranes of the target cells . In addition to P . aeruginosa, P . fluorescens, P . putida, P . fragi, and Escherichia coli were susceptible to the OM permeability-increasing action of HMP, while P . cepacia was resistant.

J Natl Med Assoc, 1989 Oct, 81(10), 1061 - 4
Saudi Arabian-American differences in antimicrobial resistance of Escherichia, Klebsiella, and Pseudomonas; Qadri SM et al.; Increasing microbial resistance to newly developed antibiotics has been a limiting factor in the therapeutic use of these agents . To determine the extent of the problem, in vitro antimicrobial susceptibility of 7,140 clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa to seven commonly used antibiotics was established at the 1,700-bed Riyadh Central Hospital in Saudi Arabia and compared with 5,513 isolates at the Oklahoma Memorial Hospital and Veterans Administration Medical Center, Oklahoma City, Oklahoma . Escherichia coli and Pseudomonas aeruginosa at Riyadh Central Hospital were generally more resistant to ampicillin, carbenicillin, gentamicin, and trimethoprim-sulfamethoxazole than those at Oklahoma Memorial Hospital and the Veterans Administration Medical Center . All 1,022 isolates of Klebsiella pneumoniae at Oklahoma Memorial Hospital were more sensitive to the antibiotics than those at Riyadh Central Hospital or the Veterans Administration Medical Center . The sensitivity pattern of Klebsiella pneumoniae at Riyadh Central Hospital and the Veterans Administration Medical Centers was similar.

Infect Control Hosp Epidemiol, 1989 Oct, 10(10), 447 - 50
Pseudomonas aeruginosa infections associated with use of povidone-iodine in patients receiving continuous ambulatory peritoneal dialysis; Goetz A et al.; Fifteen episodes of infection due to Pseudomonas aeruginosa, including peritonitis and catheter site infections, occurred in nine patients receiving continuous ambulatory peritoneal dialysis over a 27-month period . Eight episodes were associated with catheter loss . Occurrence of P aeruginosa infection was significantly associated with use of povidone-iodine solution to cleanse the catheter site . There was no association with use of povidone-iodine solution to disinfect tubing connections, use of other skin care products or exposure to other environmental sources of P aeruginosa . Cultures of available povidone-iodine products were negative . Local irritation and alteration in skin flora caused by antiseptic solution or low-level contamination of povidone-iodine solution are potential mechanisms of infection.

J Clin Invest, 1989 Oct, 84(4), 1302 - 13
Complement receptor expression on neutrophils at an inflammatory site, the Pseudomonas-infected lung in cystic fibrosis; Berger M et al.; Activation of human neutrophils (PMN) is accompanied by rapid upregulation of CR1, the C3b receptor, and CR3, the iC3b receptor, which also serves as the PMN's major adherence protein . This is necessary for migration and phagocytosis, but the extent of expression of these proteins on PMN at inflammatory sites has not been determined . We used monoclonal antibodies and flow cytometry to assess CR1 and CR3 expression on PMN in bronchoalveolar lavage (BAL) fluid of cystic fibrosis (CF) patients chronically infected with pseudomonas and in sterile joint fluid of arthritis patients . Resting peripheral blood PMN from these patients and normals expressed similar low levels of CR1 and CR3, and the patients' PMN increased CR1 and CR3 expression normally when stimulated in vitro . CR3 expression on CF BAL PMN was 90 +/- 12% of that on the same patient's blood cells stimulated in vitro with FMLP . In contrast, CR1 expression on BAL PMN was only 27 +/- 8% of that on stimulated blood cells . Similar results were obtained for joint PMN . This pattern could be reproduced in vitro by treating FMLP-stimulated blood cells with BAL supernatants or with pseudomonas or PMN elastase . The serine protease inhibitors, PMSF and alpha 1-antitrypsin prevented the lavage supernatant from reducing CR1 expression, while metalloprotease inhibitors had no effect . Treatment of PMN with elastase in vitro decrease their ability to kill opsonized Pseudomonas aeruginosa . These results suggest that PMN at inflammatory sites have maximally upregulated expression of their complement receptors, but that CR1 is then cleaved by proteolysis in situ . Although not related to the basic defect in CF, this may interfere with efficient phagocytosis and contribute to the CF patient's inability to eradicate chronic lung infection.

J Bacteriol, 1989 Oct, 171(10), 5304 - 13
Differential regulation by iron of regA and toxA transcript accumulation in Pseudomonas aeruginosa; Frank DW et al.; Iron regulation of toxA and regA transcript accumulation was examined in Pseudomonas aeruginosa PA103 containing the regA gene on a multicopy plasmid . The patterns of transcript accumulation for toxA and regA were found to be positively correlated . Dot blot and Northern (RNA) blot analysis of total RNA isolated throughout the bacterial growth cycle indicated that multiple copies of the regA gene uncoupled iron repression of the first phase of transcript accumulation for both regA and toxA genes . However, regulation by iron of the second phase of transcript accumulation for each gene was unaffected by several regA gene copies . Total toxin production was increased in cells with multiple copies of regA grown in either low- or high-iron medium . Primer extension analysis of regA mRNA extracted from cells grown in high- and low-iron medium and examined at different points in the cell growth cycle supported the hypothesis that iron regulation of regA transcription occurs at the level of transcriptional initiation . Two start sites were shown for regA transcription at -164 and -75 base pairs from the ATG start codon . The differential regulation of regA transcript accumulation when regA is present in single or multiple copy and the mapping of independent start sites for regA mRNA support the evidence that regA transcription is directed by independently regulated promoter regions.

Biochem Biophys Res Commun, 1989 Sep 29, 163(3), 1312 - 8
Identification of RegA protein from Pseudomonas aeruginosa using anti-RegA antibody; Zimniak L et al.; The product of Pseudomonas aeruginosa regA gene acts as a positive regulator of exotoxin A expression . The protein, RegA, was overproduced in E . coli transformed with an expression vector containing the regA gene . The overproduced RegA accumulated in E . coli in the form of inclusion bodies . The latter were isolated and served as a source of antigen for raising polyclonal antibodies . The antibodies reacted specifically with a P . aeruginosa protein whose molecular weight corresponded to that predicted for RegA from its known DNA sequence, and whose response to modulating factors matched that expected for RegA . The immunodetectable RegA was localized in the membrane fraction of P . aeruginosa strain PA103.

J Biol Chem, 1989 Sep 15, 264(26), 15569 - 73
The structure and serologic distribution of an extracellular neutral polysaccharide from Pseudomonas aeruginosa immunotype 3; Kocharova NA et al.; Previous work has described small molecular weight neutral polysaccharides from isolates of Pseudomonas aeruginosa that appear to be associated with the lipopolysaccharide (LPS) and distributed across serologic barriers defined by antibody to the O side chain . We have isolated and characterized another of these structures obtained from culture supernatants of an immunotype 3 strain of P . aeruginosa . The isolated neutral polysaccharide has a tetrasaccharide repeat unit: (formula; see text) where Rha is rhamnose . The structure was determined by 1H and 13C nuclear magnetic resonance spectroscopy including nuclear Overhauser enhancement experiments, acid hydrolysis, methylation analysis, Smith degradation, and optical rotation determinations . Polyclonal antibodies raised to intact and alkali-treated (0.1 N NaOH, 56 degrees C, 2 h) LPS from the seven Fisher immunotype strains of P . aeruginosa bound well to the neutral polysaccharide . Antibodies affinity purified from these sera using immobilized neutral polysaccharide as well as a neutral polysaccharide-specific monoclonal antibody, E87, reacted with an antigenically similar structure found among many isolates of different LPS serotypes in a colony blot and with LPS from the seven Fisher immunotypes in an immunoblot . In an immunoblot assay, the neutral polysaccharide inhibited binding of the monoclonal antibody, E87, to material present in LPS preparations from a variety of serotypes . This structure may represent another P . aeruginosa neutral polysaccharide variant found associated with the LPS.

Hosp Pharm, 1989 Oct, 24(10), 814 - 20, 823-6, 842
Focus on oral ciprofloxacin; clinical and economic considerations; Pastel D; Ciprofloxacin, a recently released oral fluorinated quinolone structurally related to nalidixic acid, joins norfloxacin as the second drug of this class to be released . Ciprofloxacin has a wide spectrum of antimicrobial activity and importantly demonstrates little cross resistance to non-quinolone drug classes (e.g . ureidopenicillins, cephalosporins, monobactams, carbapenems, aminoglycosides) . Unlike other antibacterial classes such as the beta-lactams or aminoglycosides, ciprofloxacin does not suffer from transferable plasmid-mediated (i.e . R-factor) antibiotic resistance . Against gram-positive (including penicillin-resistant and methicillin-resistant staphylococci aureus) and gram-negative aerobic bacteria including Pseudomonas aeruginosa, ciprofloxacin demonstrates excellent activity . Ciprofloxacin is inactive against Trichomonas sp., treponemes, and fungi and anaerobes are considered resistant . Ciprofloxacin is rapidly absorbed from the gastrointestinal tract (i.e . 70-80% bioavailable), demonstrates extensive extravascular distribution, and its 3.5-5 hour half-life allows twice daily dosing . The bacteriologic and clinical efficacy of oral ciprofloxacin was shown to be comparable to third generation cephalosporins or aminoglycosides for osteomyelitis, cefotaxime for skin structure infections, and to a combination of tobramycin with azlocillin for pulmonary exacerbation of cystic fibrosis . Adverse events associated with ciprofloxacin are related mostly to gastrointestinal disturbance and consist of nausea/vomiting or diarrhea . Concomitant administration of ciprofloxacin and theophylline may lead to decreased theophylline clearance and necessitates periodic measurements of theophylline levels to avoid toxic levels . Treatment with oral ciprofloxacin should offer substantial cost savings over a variety of parenteral antimicrobial regimens (e.g . aminoglycoside + beta-lactams) for difficult to treat infections such as chronic pyelonephritis, osteomyelitis, and skin structure infections . Consideration of important precautions (e.g . contraindications, drug interactions) and potential disadvantages (e.g . emergence of resistance) must also guide the rational use of oral ciprofloxacin.

J Biol Chem, 1989 Sep 5, 264(25), 15151 - 6
A dipeptide insertion in domain I of exotoxin A that impairs receptor binding; Chaudry GJ et al.; Deletions within the structural exotoxin A gene of 27 or 119 amino acids in domain I of the mature polypeptide, or of 88 or 105 amino acids in domains I and II, resulted in the synthesis of exotoxin A (ETA) polypeptides that were not secreted from Pseudomonas aeruginosa hosts but were localized in the cell membrane . Insertions of a hexanucleotide sequence, either pCGAGCT or pCGAATT, at TaqI sites within the gene resulted in variant exotoxin A polypeptides which were secreted normally . pCGAGCT causes insertion of either Glu-Leu or Ser-Ser in the amino acid sequence of the toxin, while pCGAATT causes insertion of either Glu-Phe or Asn-Ser dipeptides . Although the cytotoxicity of eight variants was unimpaired, that of four others was reduced, and one variant which had a Glu-Phe insert between residues 60 and 61 (ETA-60EF61) was 500-fold less cytotoxic than wild-type exotoxin A . Purified ETA-60EF61 dissociated much faster from mouse LMTK- cells than wild-type ETA, suggesting that the insertion impaired the ability of ETA-60EF61 to interact with exotoxin A receptors . The location of the insert is within a major concavity on the surface of domain I of the exotoxin A molecule, suggesting that this concavity is important for toxin-receptor interaction.

J Biol Chem, 1989 Sep 5, 264(25), 14869 - 73
Biochemical analysis of CRM 66 . A nonfunctional Pseudomonas aeruginosa exotoxin A; Galloway DR et al.; Pseudomonas aeruginosa exotoxin A (ETA) is an ADP-ribosyltransferase which inactivates protein synthesis by covalently attaching the ADP-ribose portion of NAD+ onto eucaryotic elongation factor 2 (EF-2) . A direct biochemical comparison has been made between ETA and a nonenzymatically active mutant toxin (CRM 66) using highly purified preparations of each protein . The loss of ADP-ribosyltransferase activity and subsequent cytotoxicity have been correlated with the presence of a tyrosine residue in place of a histidine at position 426 in CRM 66 . In the native conformation, CRM 66 demonstrated a limited ability (by a factor or at least 100,000) to modify EF-2 covalently and lacked in vitro and in vivo cytotoxicity, yet CRM 66 appeared to be normal with respect to NAD+ binding . Upon activation with urea and dithiothreitol, CRM 66 lost ADP-ribosyltransferase activity entirely yet CRM 66 retained the ability to bind NAD+ . Replacement of Tyr-426 with histidine in CRM 66 completely restored cytotoxicity and ADP-ribosyltransferase activity . These results support previous findings from this laboratory (Wozniak, D . J., Hsu, L.-Y., and Galloway, D . R . (1988) Proc . Natl . Acad . Sci . U . S . A . 85, 8880-8884) which suggest that the His-426 residue of ETA is not involved in NAD+ binding but appears to be associated with the interaction between ETA and EF-2.

Jpn J Antibiot, 1989 Sep, 42(9), 1926 - 37
{Clinical evaluation of a combination therapy with aztreonam and clindamycin for severe infections in leukemia and related disorders}; Tsuda S et al.; A combination of aztreonam (AZT) and clindamycin (CLDM) was evaluated for severe infections associated with leukemia and related disorders . AZT is a monobactam antibiotic which has strong bactericidal effect against Gram-negative bacteria including Pseudomonas aeruginosa . CLDM which has strong antibacterial spectrum against Gram-positive and anaerobic bacteria, was chosen as a partner of AZT in order to complement the weak points of AZT . Fifty six patients were treated with the combination therapy . Among them, 51 patients were evaluable for the effectiveness . Five patients were excluded from the evaluation because 3 patients were subjected to additional therapy with other agents such as amikacin, miconazole and pulse therapy of a large dose of methylprednisolone, one had a fever episode apparently due to primary disease, and the remaining one was discontinued of the combination therapy of administration due to mild nausea after 3 days . Excellent responses were obtained in 17 (33.3%) patients and good responses in 20 (39.2%) patients, with a total rate of effectiveness of 72.5% . One patient with whom the combination therapy was stopped due to nausea, was included in the final evaluation of side effects . Side effects were observed in 2 patients of 50 and 40 years of ages (2/52, 3.8%), both of whom suffered with nausea . In the 50 years patient of acute myeloblastic leukemia, nausea occurred in a slight degree in 3 hours after the combined regimen was started . But, it disappeared during the continuation of the combination therapy . In the 40 years patient of acute myelomonocytic leukemia, mild nausea occurred after 3 day administration of the combined regimen . It disappeared soon after the cessation of the treatment . These results indicated that a combination of AZT and CLDM was an effective and safe regimen for the treatment of severe infections in patients with hematological disorders.

J Antimicrob Chemother, 1989 Sep, 24(3), 447 - 53
A prospective study of ofloxacin in acute exacerbations of chronic respiratory disease associated with Pseudomonas aeruginosa; Meek JC et al.; Forty patients (32 inpatients and 8 outpatients) with acute purulent exacerbations of obstructive respiratory disease associated with Pseudomonas aeruginosa were treated orally with 800 mg ofloxacin twice daily for seven days . Sputum was cultured before, during and after treatment . The drug was extremely well tolerated, only one patient discontinuing because of alleged nausea . The infection was completely eradicated, with excellent clinical results and negative sputum cultures, in 23 patients . In six others the Ps . aeruginosa infection was cleared although reinfection with different organisms followed . Five patients showed recurrence of the infection after apparent initial eradication, but Ps . aeruginosa persisted in three others . Three patients were not evaluable because of death, transfer elsewhere, or discontinuation . There was a slight tendency for the mean MICs to rise during treatment, owing to eradication of all highly sensitive strains . Resistance did not develop . These results suggest that purulent exacerbations of chronic respiratory disease caused by Ps . aeruginosa can safely be treated orally with 800 mg ofloxacin twice daily, but that further studies in outpatients should be performed.

J Burn Care Rehabil, 1989 Sep-Oct, 10(5), 421 - 4
Therapeutic efficacy of timentin and augmentin versus silvadene in burn wound infections; Heggers JP et al.; Successful closure of thermal injuries, by either skin graft or delayed wound closure, largely depends on the ability to control the number of bacteria in the wound . The purpose of this study was to investigate the efficacy of two new antimicrobial agents, ticarcillin and clavulanate (Timentin) and amoxicillin and clavulanate (Augmentin), in the infected thermal injury . The therapeutic results were compared with the model treated with the standard topical silver sulfadiazine (Silvadene) . Seventy-six Sprague-Dawley rats received a 20% full-thickness thermal injury and were then divided into six treatment groups . Three of the groups were inoculated topically with 10(8) Pseudomonas aeruginosa/ml, and three of the groups received topical inoculation of 10(8) Staphylococcus aureus/ml . The groups inoculated with P . aeruginosa received either intraperitoneal Timentin, topical Silvadene, or placebo treatment . The groups inoculated with S . aureus were treated with either enteral Augmentin, topical Silvadene, or placebo . The animals received 10 days of therapy and underwent tissue biopsies on alternate days . Statistical analysis showed that the level of bacteria in the wounds compared with the control group was significantly (p less than 0.05) decreased for both antibiotics tested as measured by quantitative wound biopsies . These studies demonstrate the efficacy of systemic Timentin and Augmentin in the infected thermal injury.

Cornea, 1989 Sep, 8(3), 195 - 9
Gentamicin-resistant pseudomonal infection . Rationale for a redefinition of ophthalmic antimicrobial sensitivities; Ormerod LD et al.; Eight pseudomonal species were involved in 106 invasive infections of the eye; all were community acquired . Eighteen percent of the total and 9% of the Pseudomonas aeruginosa strains were gentamicin resistant, as defined using conventional criteria . All 10 cases of "resistant" pseudomonal (nine P . aeruginosa) keratitis responded satisfactorily to treatment with gentamicin . The resistance breakpoint (defined by safe serum levels in parenteral therapy) for most P . aeruginosa is much lower than ocular gentamicin levels achievable by optimal local application . We argue for a specific ophthalmologic definition of antibiotic resistance in infections of the cornea and external eye . MIC quantitative determinations of ocular isolates would provide more useful information to ophthalmologists than conventional qualitative disc sensitivity testing.

J Infect Dis, 1989 Sep, 160(3), 483 - 9
Treatment of experimental Pseudomonas aeruginosa pneumonia with a human IgM monoclonal antibody; Hector RF et al.; A human IgM monoclonal antibody (MA-1C1) to Fisher immunotype 3 Pseudomonas aeruginosa lipopolysaccharide antigen was evaluated for in vivo activity in a guinea pig model of experimental pneumonia . Pharmacokinetics of MA-1C1 were compared in infected and noninfected animals . Intravenous bolus infusion of MA-1C1, 1 mg/kg, resulted in peak serum antibody concentrations of 3.8 +/- 0.08 and 3.7 +/- 0.05 micrograms/ml in infected and noninfected animals, respectively . Serum half-lives were 25 and 22 h in infected and noninfected groups . Treatment with a single intravenous infusion of MA-1C1 improved survival from pneumonia and was effective over a broad dose range (0.1-2.5 mg/kg) . Cumulative survivals were 18 of 47 in the MA-1C1 group and 0 of 31 in controls (P less than .001) . Treatment with MA-1C1 also resulted in fewer positive blood cultures 12 h after infection (P = .04) . Although MA-1C1 penetrated into inflamed bronchial fluids, local concentrations were only 5% of the concentrations achieved in serum . Thus, MA-1C1 seems to provide significant therapeutic activity against experimental P . aeruginosa pneumonia by preventing dissemination of infection from the lung.

Pediatr Infect Dis J, 1989 Sep, 8(9 Suppl), S117 - 9; discussion S128-32
The use of aztreonam in the cystic fibrosis patient; Matsen JM et al.; Eradication of pulmonary infection by Pseudomonas aeruginosa in cystic fibrosis (CF) patients has long presented a significant challenge to the medical community . Many antimicrobial agents have proved incompletely effective against this persistent pathogen, and even the aminoglycosides, which represent the traditional therapy for such infections, have been associated with considerable toxicity and resistance . The monobactam antibacterial agent aztreonam is used both as single-agent therapy and in combination with other drugs . Several controlled, clinical trials have demonstrated the efficacy of aztreonam in the treatment of CF patients with pulmonary exacerbations caused by P . aeruginosa . The only side effect of aztreonam therapy commonly encountered in these studies was elevation of hepatic transaminase concentrations; this effect was of uncertain significance . It was concluded that aztreonam may offer clinical efficacy comparable to that provided by the combination of tobramycin plus azlocillin . Further, there does not seem to be any appreciable difference in the development of resistance to aztreonam compared with traditional therapies.

Eur J Cancer Clin Oncol, 1989 Sep, 25(9), 1359 - 64
Immunotherapy of gram-negative infections in oncological patients; Glauser MP; While it is widely recognized that gram-negative bacteria (GNB) are a leading cause of morbidity and mortality among patients whose immune defenses are compromised both by their underlying malignancy as well as by its treatment, efforts to prevent or to treat such infections by immunological means have been hampered for several reasons . First, the natural anatomical barriers are often disrupted either by the tumor itself, by the chemotherapeutic agents, or, as recognized more recently, by viral (herpetic) or fungal infections, so that entrance of the gram-negative flora into the host tissue and blood stream is greatly facilitated . Efforts to diminish the bacterial load by means of oral decontamination, be it selective or not, to prevent such ingress have brought limited success . Second, active immunization is not likely to elicit a useful response in these patients, so that mainly passive immunotherapy has been considered and studied . However, since the most immunocompromised cancer patients are very often leucopenic, the opsono-phagocytic function of passively administered antibodies is not likely to help the patients to get rid of the invading gram-negative bacteria . This latter observation has been particularly well established in the case of Pseudomonas aeruginosa infections in leukemic patients (Young LS, Stevens P, Ingram J . J Clin Invest 1975, 56, 850-861).

Infection, 1989 Sep-Oct, 17(5), 311 - 5
Comparative efficacy of ciprofloxacin, azlocillin, imipenem/cilastatin and tobramycin in a model of experimental septicemia due to Pseudomonas aeruginosa in neutropenic mice; Ulrich E et al.; The in vivo activity of ciprofloxacin against Pseudomonas aeruginosa was studied in a septicemia model in neutropenic mice and compared to that of other antibiotics with established activity against P . aeruginosa . When given as a single agent, ciprofloxacin proved to be as effective as imipenem/cilastatin, whereas azlocillin and tobramycin were rather ineffective . After infection with higher challenge inocula, combinations of two (synergistic) antibiotics were more effective than single agent therapy in most instances . The combination of ciprofloxacin with azlocillin was at least as effective as that of imipenem/cilastatin with tobramycin . Selection of mutants with decreased sensitivity to ciprofloxacin occurred during therapy, however, post-therapy MICs of ciprofloxacin did not exceed a level of 1 mg/l and rises of MICs did not detrimentally influence treatment outcome . Taken together with the results of earlier studies, our data encourage the use of ciprofloxacin in gram-negative septicemia in neutropenic patients.

Thorax, 1989 Sep, 44(9), 739 - 42
Infective respiratory exacerbations in young adults with cystic fibrosis: role of viruses and atypical microorganisms; Ong EL et al.; Thirty six adults with cystic fibrosis were studied over one year to determine the incidence of infection with respiratory viruses and atypical organisms . Nineteen patients entered the study during an acute exacerbation of respiratory symptoms with an increase in purulent sputum production, cough, or breathlessness accompanied by a fall in FEV1 (group 1); 17 patients entered when they were stable both clinically and in terms of lung function values (group 2) . Group 1 patients had a mean of 2.6 (range 1-4) infective exacerbations during the year and group 2 patients a mean of 1.1 (0-2) exacerbations . Eleven patients developed serological evidence of viral (influenza virus A and B, cytomegalovirus, human rhinovirus 2, adenovirus) or Mycoplasma pneumoniae infection . There was no difference in seroconversion rates between group 1 (five patients) and group 2 (six patients) . There was a weak association between viral seroconversion and the isolation of Pseudomonas aeruginosa from sputum, though this was not significant.

Gene, 1989 Sep 1, 81(1), 25 - 34
The activity of the Pseudomonas aeruginosa pilin promoter is enhanced by an upstream regulatory site; Pasloske BL et al.; Recently, a comparison of the nucleotide sequences upstream of the structural pilin genes (pil) from five different isolates of Pseudomonas aeruginosa identified a sequence homologous to a NifA-binding site, a positive regulatory sequence in Klebsiella pneumoniae which controls the expression of the genes which fix nitrogen {Pasloske et al., J . Bacteriol . 170 (1988) 3738-3741} . This sequence was located between -98 and -114 bp relative to the transcription start point . To establish whether this putative recognition sequence exerted any regulatory effect on pil gene expression, we assayed for the expression of pilin and pili, and assessed the strength of the pilin promoter with and without this upstream sequence . A 48-bp deletion, which removed the putative recognition sequence, decreased the levels of pilin and pilus expression . Also, the equivalent deletion reduced pilin promoter activity by 90% when it was measured using a promoter probe vector . These results provide evidence that a nucleotide sequence upstream of the pilin promoter positively regulates the transcription of the P . aeruginosa pil gene.

Infect Immun, 1989 Sep, 57(9), 2764 - 70
Cross-reactivity of Pseudomonas aeruginosa antipilin monoclonal antibodies with heterogeneous strains of P . aeruginosa and Pseudomonas cepacia; Saiman L et al.; Much of the morbidity and mortality in patients with cystic fibrosis (CF) is secondary to pulmonary infections with Pseudomonas aeruginosa and, more recently, with Pseudomonas cepacia . Prevention of colonization and subsequent infection would be a useful therapeutic strategy . The pili (fimbriae) of P . aeruginosa are a potential vaccine antigen, as they have been implicated in binding to respiratory epithelium and appear to have limited antigenic diversity . Monoclonal antibodies (MAbs) raised to P . aeruginosa pilin demonstrated significant cross-reactivity, as four of five P . aeruginosa strains with known pilin sequences and 10 of 15 P . aeruginosa clinical isolates hybridized by immunoblot with at least one of the three MAbs tested . The P . cepacia strains demonstrated minimal cross-reactivity with these MAbs, as only 2 of 16 strains hybridized immunologically . The three MAbs decreased the adherence of 35S-labeled P . aeruginosa PA1244 to bovine tracheal cells by 56, 45, and 31% . One of these MAbs decreased the adherence of strains P . aeruginosa PAO1 and P . cepacia 249 to CF epithelial cells by 46 and 25%, respectively . While antibodies to Pseudomonas pili must be shown to be protective in patients with CF, these studies give support for a multivalent vaccine strategy using P . aeruginosa pilin as the immunogen.

Antimicrob Agents Chemother, 1989 Sep, 33(9), 1435 - 42
Cell surface changes in Pseudomonas aeruginosa PAO4069 in response to treatment with 6-aminopenicillanic acid; Godfrey AJ et al.; Pseudomonas aeruginosa PAO4096 was induced for beta-lactamases with 6-aminopenicillanic acid . Surface changes concomitant with beta-lactamase induction were monitored . The surface hydrophobicity of the culture increased during exposure to 6-aminopenicillanic acid . The increase was associated with a change in the distribution of the O antigen in the lipopolysaccharide of treated cells . The hydrophobicity change was reversible and partially inhibited by depressed protein synthesis . The susceptibility of induced cells to rifampin was increased transiently, suggesting increased permeability of the induced cells.

J Antimicrob Chemother, 1989 Sep, 24 Suppl A, 149 - 59
Comparative activity of meropenem against Pseudomonas aeruginosa strains with well-characterized resistance mechanisms; Livermore DM et al.; Four major mechanisms cause resistance to beta-lactams in Pseudomonas aeruginosa: (i) cell wall impermeability gives broad-spectrum intrinsic resistance to all beta-lactams except imipenem, (i) loss of D-group outer membrane proteins correlates with narrow spectrum imipenem resistance, (iii) plasmid mediated beta-lactamases compromise antipseudomonal penicillins, cefoperazone and cefsulodin, and (iv) chromosomal beta-lactamase hyper-production compromises most beta-lactams except carbenicillin and imipenem . Meropenem was tested in vitro against P . aeruginosa isolates, mutants and transconjugants with these mechanisms . Meropenem had impaired activity (MIC 1-2 mg/l compared to 0.25 mg/l for sensitive isolates) for organisms with broad-spectrum intrinsic resistance . MICs of meropenem also were elevated (to 1-2 mg/l) for mutants with D2-protein-deficiency-associated imipenem resistance . Most plasmids encoding TEM, OXA or PSE beta-lactamases did not increase the MIC (0.12 mg/l) of meropenem for P . aeruginosa PU21 . Decreased susceptibility (MIC 4 mg/l), however, was observed when plasmids coding the uncommon NPS-1, PSE-2 and OXA-3 enzymes were present in this strain . MICs of meropenem remained identical for chromosomal beta-lactamase-inducible P . aeruginosa strains and their enzyme-derepressed and basal mutants, indicating that the chromosomal beta-lactamase could not protect against the new carbapenem, regardless of its mode of expression.

Infect Immun, 1989 Sep, 57(9), 2591 - 6
Effects of pyocyanine, a phenazine dye from Pseudomonas aeruginosa, on oxidative burst and bacterial killing in human neutrophils; Muller PK et al.; The effects of pyocyanine (phenazinium, 1-hydroxy-5-methyl-hydroxide, inner salt) on oxidative burst in human polymorphonuclear leukocytes were studied by several different approaches . In a cell- and enzyme-free system, pyocyanine oxidized NADPH . The reduced pyocyanine could be measured by its reaction with ferricytochrome c . It was shown by this assay that resting as well as phorbol myristate acetate- or zymosan-stimulated granulocytes reduced pyocyanine . The effect was independent of mitochondria, as cytoplasts were similarly active . Measurement of the hexose monophosphate shunt in intact granulocytes in the presence of pyocyanine indicated a concentration-dependent activation of the shunt without the generation of O2-, suggesting that pyocyanine oxidizes NADPH to NADP+ when it enters granulocytes . Intracellular NADPH in granulocytes was indeed lowered by almost 40% after incubation with pyocyanine . It is by this shuttling of reduction equivalents, leading to the partial depletion of NADPH, that pyocyanine affects the observed concentration-dependent partial inhibition of the phorbol myristate acetate- and zymosan-stimulated generation of O2- . A further consequence was that the intracellular killing of Staphylococcus aureus was also partially suppressed, particularly at higher loads of granulocytes with bacteria . Phagocytosis was not inhibited by pyocyanine concentrations as high as 500 microM . Pyocyanine did not affect the intracellular killing of Pseudomonas aeruginosa . The possible relevance of these findings to the course of mixed hospital infections in immunocompromised patients is discussed.

G Ital Dermatol Venereol, 1989 Sep, 124(9), 415 - 7
{Splash rash dermatitis . A case}; Schiazza L et al.; The Authors report a case of a folliculitis developed in a woman who used a spa with hydrojet circulation . This dermatitis is due to Pseudomonas aeruginosa, which can colonizes the closed-cycle water systems.

Antimicrob Agents Chemother, 1989 Sep, 33(9), 1553 - 6
In vitro bactericidal activities of gentamicin, cefazolin, and imipenem in peritoneal dialysis fluids; Halstead DC et al.; Continuous ambulatory peritoneal dialysis is an important modality of therapy for patients with renal disease . However, peritonitis continues to be a major risk factor and is usually treated by intraperitoneal administration of antimicrobial agents . Few data are available concerning the stability of antimicrobial agents in peritoneal dialysis solution beyond 48 h . Our investigation was designed to establish the chemical and biological stability of gentamicin alone and in combination with cefazolin in peritoneal dialysis solution at 6 and 72 h by an immunoassay and by an in vitro bactericidal test against American Type Culture Collection (Rockville, Md.) strains of Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis . In addition, uninfected peritoneal dialysis effluent was inoculated with three American Type Culture Collection strains and gentamicin or imipenem . Gentamicin alone or in combination with cefazolin was not altered chemically and was bactericidal for Staphylococcus spp . but not P . aeruginosa . In contrast, imipenem was active against both Staphylococcus spp . and P . aeruginosa . Undefined factors other than inactivation of gentamicin may be responsible for the lack of bactericidal activity and treatment failure of Pseudomonas infections.

Antimicrob Agents Chemother, 1989 Sep, 33(9), 1500 - 5
Antipseudomonal activity of simulated infusions of gentamicin alone or with piperacillin assessed by serum bactericidal rate and area under the killing curve; Tisdale JE et al.; The objectives of this study were to (i) determine which of three simulated dosing regimens (gentamicin alone, simultaneous infusions of gentamicin and piperacillin, or staggered infusions of gentamicin and piperacillin) produced the fastest killing rate of Pseudomonas aeruginosa in serum, using the serum bactericidal rate (SBR) assay; and (ii) describe an alternative method of analysis of killing curves, the area under the killing curve (AUKC) . Gentamicin alone or combined with piperacillin was added to heat-inactivated human serum to approximate drug concentrations achieved after the above-mentioned types of infusion . By a microdilution technique, seven strains of P . aeruginosa were exposed to no drug (control) and gentamicin alone or with piperacillin; colony counts were determined at hourly intervals for 5 h, and log10 CFU per milliliter was plotted versus time . Linear regression was used to calculate the slope (SBR) of each timed killing curve for each drug concentration tested alone or in combination . In addition, the AUKC for each curve was calculated . To compare simulated infusion regimens further, the cumulative AUKC (the sum of AUKCs for specific time points along the serum concentration-time curve for each simulated regimen) was calculated . With the SBR assay or AUKC determination, there was a significant increase in the rate of killing of all test strains by the combination compared with gentamicin alone only at gentamicin concentrations which exceeded the MIC (8, 5, and 2.5 micrograms/ml) . Mean cumulative AUKC of the simultaneous-infusion regimen was significantly less (indicating faster killing) than either the staggered-infusion regimen or the gentamicin infusion alone . Both the SBR and AUKC have the potential for integration of in vitro microbiologic effects and in vivo pharmacokinetics of antimicrobial agents.

J Antimicrob Chemother, 1989 Sep, 24 Suppl A, 233 - 8
The antibacterial activity of meropenem in combination with gentamicin or vancomycin; Wise R et al.; The kinetics of bacterial killing by meropenem alone and in combination with gentamicin (for Pseudomonas aeruginosa) and vancomycin (for Staphylococcus aureus) were studied for two strains of each species . Against the two strains of P . aeruginosa, meropenem at concentrations up to 4 x MIC was rapidly bactericidal--but regrowth occurred by 24 h . The addition of half the MIC of gentamicin to the MIC of meropenem led to a more rapid decline of the colony count and to the prevention of regrowth of the strain which was gentamicin-susceptible . Similar results were obtained for a methicillin-susceptible strain of S . aureus when vancomycin was added at a concentration of half the MIC . A methicillin-resistant strain also was killed by a combination of vancomycin at half the MIC plus meropenem at the MIC . The study showed that the killing action of meropenem against P . aeruginosa and staphylococci is enhanced by the addition of gentamicin or vancomycin respectively.

J Antimicrob Chemother, 1989 Sep, 24 Suppl A, 169 - 74
Bactericidal activity of meropenem against Pseudomonas aeruginosa; Yourassowsky E et al.; Ten strains of Pseudomonas aeruginosa that were susceptible to imipenem (MICs 2 mg/l) were exposed to a new parenteral carbapenem, meropenem (MIC 0.25 mg/l) . Kinetic turbidometry showed that, as with other beta-lactam antibiotics, there was a prelytic increase in the culture OD following exposure to meropenem . The maximal value of the prelytic increase in the OD was higher for meropenem than for imipenem at concentrations 0.5, 1, 2, 4 and 8 x MIC . This corresponded to the formation of short filaments during exposure to low concentrations of meropenem . These filaments remained viable for 1-2 h, according to the drug concentration . For this reason, the killing began later with meropenem than with imipenem . After this delay, the killing rate for meropenem was the same as with imipenem, but occurred with lower concentrations of meropenem.

J Antimicrob Chemother, 1989 Sep, 24 Suppl A, 161 - 7
Emergence of resistance to carbapenem antibiotics in Pseudomonas aeruginosa; Margaret BS et al.; Meropenem is a new carbapenem antibiotic with activity similar to that of imipenem . Development of resistance to imipenem by Pseudomonas aeruginosa has occurred in therapy and is associated with loss of a 45,000-48,000 molecular weight outer membrane protein (OMP) and decreased imipenem penetration . Seven pairs of isolates of P . aeruginosa obtained before treatment and after emergence of resistance were examined for changes in MIC of both imipenem and meropenem, and for changes in OMP profile . Resistant mutants were obtained also from the pre-therapy strains on Mueller-Hinton agar containing increasing amounts of either drug, and maintained under antibiotic pressure . OMP preparations of all pre- and post-therapy strains and laboratory mutants were separated by polyacrylamide gel electrophoresis . Loss of a 45,000-48,000 molecular weight protein occurred in variants selected under carbapenem pressure and in all post-therapy isolates . Meropenem remained four-fold more active than imipenem against the resistant strains and mutants.

Can J Microbiol, 1989 Sep, 35(9), 890 - 4
Flagellar antibody stimulated opsonophagocytosis of Pseudomonas aeruginosa associated with response to either a- or b-type flagellar antigen; Anderson TR et al.; Pseudomonas aeruginosa exhibit one of two flagella types: a homogeneous b type, with molecular weight of 53,000, or a heterogeneous a type (subtypes a0, a1, a2, a3, and a4), with molecular weights ranging from 45,000 to 52,000 . Pseudomonas aeruginosa flagellar antiserum was shown to promote uptake of radiolabeled bacteria by mouse polymorphonuclear leukocytes . Bacteria were detected directly associated with washed leukocytes and visualized, by electron microscopy, internalized in polymorphonuclear leukocytes . Phagocytosis was specific for the flagella type (a or b) in that homologous flagella serum enhanced uptake three to four times greater than heterologous serum or normal rabbit serum . An a-type antiserum was shown to enhance phagocytosis of four different a-type strains with varying subantigen types, indicating the presence of a common cross-reactive a0 antigen in this flagella type . Phagocytic killing of internalized bacteria was not seen with the addition of only flagellar antiserum.

Zentralbl Bakteriol, 1989 Sep, 271(3), 364 - 71
Lectin typing of Pseudomonas aeruginosa strains of different serogroups, Habs and Fisher types; Chatterjee BP et al.; Sixteen Habs and three Fisher types of Pseudomonas aeruginosa were typed with lectins of know specificity resulting from their interaction with bacterial cell surface carbohydrates as evidenced by agglutination-inhibition assay with simple carbohydrates . Lipopolysaccharides of few strains of Pseudomonas are precipitated with different lectins and the results are corroborated by those of agglutination suggesting that Pseudomonas aeruginosa can be characterized intraspecifically by lectins.

Photochem Photobiol, 1989 Sep, 50(3), 413 - 8
Photo-induced electron ejection from the reduced copper of Pseudomonas aeruginosa azurin; Corin AF et al.; The reduced form of Pseudomonas aeruginosa azurin exhibits an enhanced absorbance in the UV compared to that of the oxidized protein . This enhancement has also been observed for azurins from other bacterial species and for another type I copper protein, plastocyanin . Pulsed laser excitation of the reduced azurin in the region of enhanced absorbance at 308 nm results in single photon, rapid (less than 30 ns) oxidation of the copper center and formation of the hydrated electron with a quantum yield of 0.05 . The hydrated electron reacts in the expected manner with scavengers such as nitrous oxide, oxygen, acetone and nitromethane . In the absence of scavengers, the electron reacts with the protein, including the disulfide bond, to form the disulfide radical anion, observed at 410 nm . The overall photophysical event involves a charge-transfer to solvent transition although the existence of intermediate states can not be excluded.

J Clin Microbiol, 1989 Sep, 27(9), 1992 - 6
Epidemic Pseudomonas aeruginosa serotype O16 bacteremia in hematology-oncology patients; Richet H et al.; From 1 August 1978 through 31 December 1982, 98 hematology-oncology patients had positive cultures for Pseudomonas aeruginosa serotype O16; 22 of these patients developed bacteremia, and this bacteremia was associated with the occurrence of extensive perineal cellulitis in 10 patients (45.5%) . Seventeen bacteremic patients died . The epidemic strain differed from other P . aeruginosa organisms isolated at the hospital by its resistance to all antibiotics available at that time (ticarcillin, piperacillin, azlocillin, tobramycin, ceftizoxime, ceftriaxone, moxalactam, ceftazidime, and fosfomycin) . Univariate analysis showed the following factors to be significantly associated with P . aeruginosa O16 bacteremia: the severity of granulocytopenia at the time of the bacteremia, more days with fever, the administration of ticarcillin or an aminoglycoside, the receipt of a greater number of antimicrobial agents for a longer period of time before documentation of the bacteremia, and the occurrence of cellulitis . Logistic regression analysis showed that duration of fever, duration of bacteremia, and the number of antimicrobial agents administered before documentation of the bacteremia were the best predictors of P . aeruginosa O16 bacteremia . In a prospective study of the acquisition of P . aeruginosa by hematology-oncology patients, 1,149 specimens (throat and rectal swabs) from 270 patients and 201 specimens from their washbasin drains were collected . On only three occasions was the epidemic strain isolated from both the patient and his or her washbasin, but in each case the colonization of the patient preceded the isolation of the strain from the washbasin . The transmission of any P . aeruginosa organism from washbasin drain to patient could not be documented . Contact isolation precautions from the Centers for Disease Control were used for all hematology-oncology patients colonized or infected with P . aeruginosa after 7 January 1983 . No case of P . aeruginosa O16 bacteremia has occurred at Hotel Dieu since July 1984.

J Bacteriol, 1989 Sep, 171(9), 5173 - 5
Cloning and expression of the alkaline proteinase gene from Pseudomonas aeruginosa IFO 3455; Atsumi Y et al.; The alkaline proteinase gene from Pseudomonas aeruginosa IFO 3455 was cloned and expressed in Escherichia coli.

Arch Otolaryngol Head Neck Surg, 1989 Sep, 115(9), 1063 - 9
Efficacy of oral ciprofloxacin plus rifampin for treatment of malignant external otitis; Rubin J et al.; Malignant external otitis is an invasive pseudomonal infection characteristically afflicting the elderly patient with diabetes mellitus . Therapy has traditionally consisted of the long-term administration of combination parenteral antibiotics, but morbidity and mortality remain substantial despite this therapy . We treated 11 consecutive patients with the oral combination of ciprofloxacin (750 mg twice daily) and rifampin (600 mg twice daily) for 6 to 12 weeks (mean, 8 weeks) . Pseudomonas aeruginosa was isolated from ear canal or mastoid, and bone destruction was documented by computed tomography in all patients . Seven patients (64%) had ear irrigation before onset of the infection . Ten patients fulfilled the criteria of both clinical and bacteriologic cure . No serious adverse reaction to either antibiotic was observed . Otalgia and otorrhea responded at a mean of 6 and 4 days, respectively, following the initiation of therapy . The erythrocyte sedimentation rate fell from a mean pretherapy value of 81 mm/h (range, 41 to 138 mm/h) to 18 mm/h (range, 3 to 45 mm/h) after the completion of antibiotic therapy . Minimum inhibitory and bactericidal concentrations established that all organisms were sensitive to ciprofloxacin . Time-kill curve and checkerboard assays failed to demonstrate either synergy or antagonism between ciprofloxacin and rifampin . Serum inhibitory and bactericidal titers showed minimal increase in inhibition and killing of the bacteria with the addition of rifampin . Rifampin did not alter the pharmacokinetics of ciprofloxacin . The successful use of oral antibiotics for this difficult infection may be a major advance . Reduction in antibiotic costs and hospitalization and convenience of oral administration were of notable benefit.

Infect Immun, 1989 Sep, 57(9), 2782 - 5
Fibronectin as an enhancer of nonopsonic phagocytosis of Pseudomonas aeruginosa by macrophages; Kluftinger JL et al.; Fibronectin is capable of enhancing uptake by macrophages of Pseudomonas aeruginosa grown in vivo in rats or mice or in vitro on nutrient agar plates . It was demonstrated that concentrations as low as 27 nM fibronectin produced significant enhancement of macrophage phagocytosis . Washing of fibronectin-treated macrophages did not prevent phagocytosis enhancement, but washing of fibronectin-treated bacteria did . The tetrapeptide arginine-glycine-aspartic acid-serine, which comprises the eucaryotic cell-binding domain of fibronectin, was also capable of promoting bacterial uptake, whereas the control tetrapeptide tetraglycine was not . Fibronectin caused depolarization of the mouse macrophage cell line P388D1, plasma membrane, as demonstrated by using a polarization-sensitive fluorescent probe . These data indicate that promotion by fibronectin of nonopsonic phagocytosis is mediated by the action of fibronectin on the macrophages.

Cornea, 1989 Sep, 8(3), 225 - 6
Pseudomonas corneal ulcer after use of extended-wear rigid gas-permeable contact lens; Ehrlich M et al.; We report a bacterial corneal ulcer that occurred in a patient who had worn extended-wear rigid gas-permeable contact lenses on a 1-week cycle for 9 months . Pseudomonas aeruginosa was cultured not only from the corneal ulcer but also from the contact lens solutions, suggesting that the patient had been noncompliant with care procedures . To our knowledge, this is the first report of a bacterial corneal ulcer associated with use of a rigid gas-permeable contact lens on an extended-wear basis.

Cornea, 1989 Sep, 8(3), 188 - 90
Effect of minimal antibiotic treatment on bacterial keratitis; Hodges EJ et al.; We studied the effect of minimal antibiotic therapy on pseudomonas keratitis in rabbits . Both corneas of 12 rabbits were infected with Pseudomonas aeruginosa and treated 24 and 48 h later with two drops of tobramycin or placebo . Corneal infections in antibiotic- and placebo-treated groups were comparable in appearance 24 and 48 h after inoculation . However, bacterial recovery was significantly less in eyes treated with minimal antibiotic therapy (p = 0.009) . Although negative cultures were obtained from 11 of 12 antibiotic-treated eyes, bacteria could be recovered from eight of these culture negative corneas when corneas were ground and cultured . These studies suggest that minimal antibiotic therapy may impair bacterial recovery without completely eradicating live organisms.

Bioorg Khim, 1989 Sep, 15(9), 1253 - 8
{Regulation of proteolytic processes using antisense RNA genes htpR and lon of Escherichia coli in hetero- and homologous genetic systems}; Kiselev VI et al.; Possibility of correction of proteolytic processes in cells of Escherichia coli and Pseudomonas aeruginosa has been studied . For this purpose recombinant plasmids directing the synthesis of antisense RNAs were constructed . In Ps . aeruginosa the synthesis of htpR antisense RNA resulted in 2.5-fold reduction of the intensity of degradation of 3H-puromycin polypeptides under heat shock conditions . An antisense RNA complementary to the 5'- end of E . coli lon gene decreased the same index to the level observed in lon- mutants . Genes homologous to htpR and lon genes of E . coli were found in Pseudomonas: bacteria in hybridisation experiments . This finding suggests that the genetic system of heat shock in these microorganisms is organized in a similar manner.

Biochim Biophys Acta, 1989 Aug 31, 997(3), 193 - 8
Phosphonoacetaldehyde hydrolase from Pseudomonas aeruginosa: purification properties and comparison with Bacillus cereus enzyme; Dumora C et al.; Phosphonoacetaldehyde hydrolase (2-oxoethylphosphonate phosphonohydrolase, EC 3.11.1.1) has been purified to electrophoretic homogeneity from cells of Pseudomonas aeruginosa A 237 grown in a culture medium containing 2-aminoethylphosphonate as both phosphorus and carbon sources . The native Mr has been estimated to be 62,000 +/- 2000, using a gel filtration column equilibrated with standard proteins . A subunit of Mr 30,000 +/- 1000 determined in sodium dodecyl sulfate-polyacrylamide gel electrophoresis gives evidence of a homodimeric structure . The enzyme, which catalyzes the C-P bond cleavage of phosphonoacetaldehyde, has a Km value of 210 microM . It is moderately inhibited by methyl-, ethyl-, propyl- and butylphosphonic acids and activated by aminomethyl-, aminoethylphosphonic acids as well as by phosphonoformic, phosphonoacetic and phosphonopropionic acids . Inhibition by orthophosphite is a time-dependent process which exhibits first-order kinetics and is enhanced by the presence of acetaldehyde . Assays for phosphite removal by dilution or dialysis do not reverse the inhibition . Phosphonoacetaldehyde hydrolase inactivation by phosphite ion appears to be inconsistent with the concept of a Schiff base intermediate as proposed for Bacillus cereus enzyme.

FEBS Lett, 1989 Aug 28, 254(1-2), 33 - 8
Nitrite reductase from Pseudomonas aeruginosa: sequence of the gene and the protein; Silvestrini MC et al.; The gene coding for nitrite reductase of Pseudomonas aeruginosa has been cloned and its sequence determined . The coding region is 1707 bp long and contains information for a polypeptide chain of 568 amino acids . The sequence of the mature protein has been confirmed independently by extensive amino acid sequencing . The amino-terminus of the mature protein is located at Lys-26; the preceding 25 residue long extension shows the features typical of signal peptides . Therefore the enzyme is probably secreted into the periplasmic space . The mature protein is made of 543 amino acid residues and has a molecular mass of 60,204 Da . The c-heme-binding domain, which contains the only two Cys of the molecule, is located at the amino-terminal region . Analysis of the protein sequence in terms of hydrophobicity profile gives results consistent with the fact that the enzyme is fully water soluble and not membrane bound; the most hydrophilic region appears to correspond to the c-heme domain . Secondary structure predictions are in general agreement with previous analysis of circular dichroic data.

J Immunol Methods, 1989 Aug 15, 122(1), 51 - 7
Determination of the components of immune complexes made in vitro with antigens derived from Pseudomonas aeruginosa; Kronborg G et al.; A method for identification of the components of immune complexes would increase our understanding of the pathogenesis of chronic diseases such as Pseudomonas aeruginosa lung infection in cystic fibrosis . Capillary tube, gel diffusion and turbidimetric methods of determining immune complex formation were investigated with antigens from P . aeruginosa and the homologous rabbit antisera . Visible complexes were formed in the first two methods with flagella antigens . Purified lipopolysaccharide from P . aeruginosa would not form visible precipitates and a rapid and economical turbidimetric method was developed with 96-well microtiter plates . Larger quantities of immune complexes were formed in vitro with antigen/antibody ratios determined by the above methods . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting (Western blotting) were evaluated and found to be useful in determining the antigen and antibody components of these immune complexes.

Jpn J Antibiot, 1989 Aug, 42(8), 1705 - 12
{A clinical experience of ofloxacin in patients with respiratory infection}; Tanaka K et al.; To a total of 31 patients (18 in- and 13 out-patients) having respiratory infections, we administered ofloxacin (OFLX) orally at a daily dose of 300 to 600 mg and examined its clinical effect . The clinical effect in the 31 cases was as good as 83.9% . Among these cases, 6 cases showed Pseudomonas aeruginosa, thereby indicating the effective rate of OFLX at 50% . In the present examination, we experienced cases in which OFLX-resistant P . aeruginosa appeared in the cases of long-term administration of OFLX . Therefore, our clinic carried out the sensitivity test of P . aeruginosa against OFLX, gentamicin (GM) and imipenem (IPM) in 1987, using clinically-segregated strains of P . aeruginosa obtained by sputum tests . The sensitive strains, which were 100% sensitive to OFLX, GM, IPM respectively in 1985, showed, in segregated strains in 1987, sensitivity of OFLX 57.1%, GM 85.7% and IPM 100%, thus indicating the high resistance-acquiring frequency of P . aeruginosa against OFLX.

J Chemother, 1989 Aug, 1(4), 233 - 9
Resistance to antibiotics and inorganic ions in virulent bacterial strains from a hospital; Vazquez F et al.; Virulent strains of Staphylococcus aureus, S . epidermidis, Escherichia coli and Pseudomonas aeruginosa were studied for their resistance to antibiotics and inorganic ions, the correlation with their clinical use and the usefulness as an epidemioliogical tool . Multiresistance was common, the antibiotypes were similar to those previously reported, but characteristic resistotypes endemic of our county were found . A correlation between resistance and metal ion consumption was not detected . Staphylococci strains were susceptible to vancomycin, cephalothin and mercury chloride; S . epidermidis showed higher rates of resistance to antibiotics and lower to cadmium chloride and potassium iodine than S . aureus . E . coli strains were susceptible to new beta-lactamans; resistance to cephalothin, gentamicin, tobramycin and amikacin was less than 10% . P, aeruginosa was the species with the most multiresistance and antibiotype diversity, only ceftazidime, amikacin and imipenem had a resistance rate less than 11% . In both E . coli and P . aeruginosa resistance to all tested metals (except silver nitrate) was found although with different percentages.

Scand J Immunol, 1989 Aug, 30(2), 219 - 23
Auto-antibodies to tumour necrosis factor alpha in healthy humans and patients with inflammatory diseases and gram-negative bacterial infections; Fomsgaard A et al.; A semi-quantitative immunoblotting method was developed to screen for serum auto-antibodies against tumour necrosis factor alpha (TNF alpha) . Forty nitrocellulose strips containing identical amounts of human recombinant TNF alpha (rTNF alpha) were prepared for each set-up, and the anti-TNF alpha antibody immunoreactivities were scored according to the density of the resulting colour reaction . A significant number of sera from apparently healthy donors contained detectable auto-antibodies to TNF alpha (40%), while the strongest reaction was observed in 8% . A higher prevalence of anti-TNF alpha antibodies was found in sera from patients with Gram-negative bacterial septicaemia (66%), cystic fibrosis with chronic Pseudomonas aeruginosa lung infection (72%), and various rheumatic diseases (61%) . The antibodies in sera from these patients belonged primarily to the IgG and IgM classes, the latter exhibiting the strongest response . Longitudinally collected serum samples from patients in septic endotoxin shock revealed that the anti-TNF alpha antibodies were induced initially during septicaemia, reaching maximum reactivities within the first week and returning to low or undetectable levels on days 9-20.

J Am Acad Dermatol, 1989 Aug, 21(2 Pt 1), 200 - 4
Treatment of scleroderma skin ulcers with a hydrocolloid membrane; Milburn PB et al.; The purpose of this study was to determine the usefulness of hydrocolloid membrane dressings in the treatment of finger and hand ulcers of scleroderma (progressive systemic sclerosis) . Ten pairs of ulcers occurring in seven patients were studied . The ulcers in each patient were treated in a paired comparison trial: one ulcer in each pair was treated with a hydrocolloid membrane; the other was a control . Treatment was continued until at least one ulcer of each pair was healed . The rate of healing of the hydrocolloid membrane-treated ulcers was significantly faster than that of the control ulcers . Pain was rapidly and dramatically reduced in all hydrocolloid membrane-treated ulcers . An infection caused by Pseudomonas aeruginosa occurred in a hydrocolloid membrane-treated ulcer but rapidly responded to topical therapy . Hydrocolloid membrane treatment of sclerodermatous hand ulcers appears to be an effective method of accelerating healing and reducing pain.

Chem Pharm Bull (Tokyo), 1989 Aug, 37(8), 2103 - 8
Studies on antibacterial agents . I . Synthesis of substituted 6,7-dihydro-1-oxo-1H,5H-benzo{i,j}quinolizine-2-carboxylic acids; Ishikawa H et al.; A series of substituted 6,7-dihydro-1-oxo-1H,5H-benzo{i,j}quinolizine-2-carboxylic acids was synthesized and tested for antibacterial activities . Among them, 9-fluoro-6,7-dihydro-5-methyl-8-(4-methyl-1-piperazinyl)-1-oxo-1H,5H- benzo{i,j}quinolizine-2-carboxylic acid (OPC-7241) exhibited potent antibacterial activity against gram-positive and -negative bacteria, including Staphylococcus aureus and Pseudomonas aeruginosa, and 9-fluoro-6,7-dihydro-8-(4-hydroxy-1-piperidyl)-5-methyl-1-oxo-1H, 5H-benzo{i,j}quinolizine-2-carboxylic acid (OPC-7251) showed potent activity characteristically against Propionibacterium acnes.

Zh Mikrobiol Epidemiol Immunobiol, 1989 Aug, (8), 12 - 4
{The protective effect of preparations made from plant seedlings in experimental Pseudomonas aeruginosa infection}; Khaitov RM et al.; 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.

J Hosp Infect, 1989 Aug, 14(2), 99 - 105
An outbreak of multiply resistant Pseudomonas aeruginosa in a neonatal unit: plasmid pattern analysis; Garcia DC et al.; An outbreak of infection due to multiply resistant Pseudomonas aeruginosa occurred from March to April 1986 in a neonatal unit . Affected neonates were receiving ventilation support and the mortality rate was high . Plasmid analysis and antibiograms indicated that the outbreak was due to a single strain . A survey of bacteria isolated from respirators, potable water and hands of personnel working in the unit failed to recover the outbreak strain . Lack of sterilization of respirators and overcrowding were considered to be the causes of the outbreak and reinforcement of the importance of aseptic techniques helped in its termination.

Malays J Pathol, 1989 Aug, 11, 43 - 7
Susceptibility of non-fermentative gram-negative organisms to ureidopenicillins and quinolones; Moosdeen F et al.; The susceptibility of non-fermentative Gram-negative bacteria (excluding Pseudomonas aeruginosa) to ureidopenicillins and new quinolones was investigated . The ureidopenicillins were not active against the strains except against Pseudomonas species, 90% of which were inhibited by 64 mg/l . The new quinolones, particularly ciprofloxacin, had excellent activity (MIC range 0.06-8 mg/l) against these strains which included those resistant to beta-lactams and aminoglycosides . This suggested a promising alternative group of compounds to be used in chemotherapy of infections caused by non-fermenters.

Microb Pathog, 1989 Aug, 7(2), 147 - 52
Pseudomonas aeruginosa exotoxin A primes human monocyte oxidative burst response in vitro; Patzer J et al.; Modulation of the oxidative burst responsiveness of human blood monocytes and neutrophils after incubation with purified exotoxin A from Pseudomonas aeruginosa was studied in a lucigenin- and luminol-enhanced chemiluminescence system . Exotoxin A alone caused a dose-dependent stimulation of monocyte chemiluminescence responses, whereas neutrophil responses were inconsistent . Preincubation of monocytes with exotoxin A primed the cells for a significantly higher oxidative burst response when N-f-methionyl-leucyl-phenylalanine (fMLP) was used as a secondary stimulus, especially in the lucigenin-enhanced system . Heat-treatment at 100 degrees C for 15 min completely abolished the priming activity of the exotoxin A preparation . These findings demonstrate that exotoxin A modulates monocyte responsiveness in the chemiluminescence assay and suggest that increased release of toxic oxygen radicals from mononuclear phagocytes may contribute to the tissue damage in lungs with chronic P . aeruginosa infections.

FEMS Microbiol Lett, 1989 Aug, 51(3), 327 - 32
Uptake of 14C-chlorhexidine diacetate to Escherichia coli and Pseudomonas aeruginosa and its release by azolectin; Fitzgerald KA et al.; Uptake of 14C-labelled chlorhexidine diacetate (14C-CHA) by wild-type and envelope mutant strains of Escherichia coli and Pseudomonas aeruginosa was very rapid . Maximum uptake was observed within a contact time of 20 s with no additional binding on increased contact, and was concentration-dependent . In contrast to this rapid binding of 14C-CHA, bactericidal studies revealed that the lethal activity of low concentrations of unlabelled CHA was slow, although higher concentrations had a rapid effect . Comparison of a wild-type strain with its envelope mutants indicated that there was little difference in 14C-CHA uptake, in minimal inhibitory concentrations or in bactericidal activity . Azolectin was found to be an effective neutralising agent of biguanide action, but in in vitro agar tests and in reducing or removing the amount of 14C-CHA taken up by the cells.

J Chemother, 1989 Aug, 1(4), 226 - 30
Relationship of antibiotic resistance phenotype to the R-pyocin susceptibility pattern in clinical isolates of Pseudomonas aeruginosa; Tzouvelekis LS et al.; One hundred sixteen clinical isolates of Pseudomonas aeruginosa were collected from 7 hospitals in Athens . All strains were studied for their susceptibility to cefotaxime, ceftazidime, carbenicillin, aztreonam, imipenem, nalidixic acid, ciprofloxacin, gentamicin, and chloramphenicol . In addition, the R-pyocin susceptibility pattern was determined and the strains were O-serotyped and tested for their agglutination in acriflavine . The isolates included 53 strains resistant to both gentamicin and carbenicillin, 13 to carbenicillin only, 20 to gentamicin only, and 30 sensitive to gentamicin and carbenicillin . The multiresistant isolates displayed relatively higher resistance to all other antibiotics except aztreonam and cefotaxime . Remarkably 30 out of 53 multiresistant isolates reacted with one pyocin only, namely pyocin R2 . This R-pyocin response was not encountered in any other strains of the other antibiotic resistance phenotypes . These isolates belonged to the 0-12 serogroup . The 0-12 serogroup was represented only in a minority of strains giving other R-pyocin reactions . It is interesting that strains reacting with pyocin R5 only were mostly susceptible to antibiotics . The results clearly indicate lipopolysaccharide-core mutations in multiresistant clinical isolates of P . aeruginosa . Despite the fact that the R-pyocin resistance pattern can not define the precise possible defect, the multiple and high level resistance associated with R2-pyocin reaction seems to be an interesting trait.

Antimicrob Agents Chemother, 1989 Aug, 33(8), 1400 - 2
Antibiotic treatment and intestinal colonization by Pseudomonas aeruginosa in cancer patients; Andremont A et al.; To determine whether antibiotic treatment increases the risk of colonization by Pseudomonas aeruginosa, we performed a case-control study comparing antibiotic exposure in cancer patients colonized by P . aeruginosa and in noncolonized controls . Of 88 patients, 76 had been exposed to at least one antibiotic, but colonization was not statistically associated with exposure to any specific antibiotic treatment, administered orally or parenterally, alone or in combination.

Antimicrob Agents Chemother, 1989 Aug, 33(8), 1368 - 72
Cross-resistance of Pseudomonas aeruginosa to ciprofloxacin, extended-spectrum beta-lactams, and aminoglycosides and susceptibility to antibiotic combinations; Chow AW et al.; The susceptibilities of 270 clinical isolates of Pseudomonas aeruginosa from diverse sources (82 burn patients, 76 cystic fibrosis {CF} patients, and 112 other sources) to ciprofloxacin and three other quinolones, nine extended-spectrum beta-lactams, and three aminoglycosides were determined by an agar dilution method in cation-supplemented Mueller-Hinton medium . Ciprofloxacin, ceftazidime, imipenem, and aztreonam were the most active . MICs for burn isolates were consistently higher than those for other isolates for most antibiotics, whereas those for CF strains were consistently lower . Multidrug resistance to aminoglycosides and beta-lactams occurred in 21% of the burn isolates, 2.6% of the CF isolates, and 8.9% of the other isolates . Ninety percent of these strains remained susceptible to ciprofloxacin . Seven percent of the isolates were resistant to ciprofloxacin (MIC, greater than or equal to 2 micrograms/ml) . Concurrent resistance to ciprofloxacin and beta-lactams or aminoglycosides was rare (1.8 to 4%) . Analysis by Spearman rank correlation revealed a high degree of correlation of MICs among antibiotics within the same class, except for imipenem . An inoculum effect was observed for all antibiotics between 10(6) and 10(4) CFU (P less than 0.05), with those for piperacillin and cefoperazone being the most pronounced (16-fold and 8-fold differences, respectively), and was least apparent for the quinolones, aminoglycosides, imipenem, and aztreonam (twofold differences) . Selected strains for which there were high MICs of ciprofloxacin (greater than or equal to 1 micrograms/ml) were tested against ciprofloxacin in combination with other agents in a checkerboard agar dilution assay . Synergistic (summated fractional inhibitory concentration, </=0.5) interactions at clinically achievable concentrations were most frequent with mezlocillin (33%), piperacillin (21%), and (7.6%), aztreonam (3.7%), and the aminoglycosides (3.7%) . Antagonism (summated fractional inhibitory concentration, >/= 4) was observed in only one instance (with gentamicin).

Antimicrob Agents Chemother, 1989 Aug, 33(8), 1207 - 11
Determinants of the efficacy of tobramycin therapy against isogenic nonmucoid and mucoid derivatives of Pseudomonas aeruginosa PAO1 growing in peritoneal chambers in mice; Kelly NM et al.; Mice which were supporting the growth of Pseudomonas aeruginosa in chambers implanted in their peritoneums were given two intramuscular injections of tobramycin (15 mg/kg of body weight each) at an interval of 8 h . Three hours later, chambers were removed and their contents were assessed for viable counts . Controls revealed that tobramycin levels in the chambers were 3.8 micrograms/ml 15 min after injection of 15 mg of tobramycin per kg and remained above the in vitro MICs (0.5 to 1 microgram/ml) for the tested strains for 8 h . It was demonstrated that tobramycin therapy was less effective with higher inocula and with longer delay before administration . Thus, in vivo, the concentration of bacteria in the chambers at the time of the first tobramycin injection had a profound effect on the bactericidal efficacy of tobramycin therapy . No such concentration dependence was observed in mock in vitro therapy experiments . A phage-selected mucoid derivative of P . aeruginosa PAO1 showed only a marginal increase in in vitro aminoglycoside susceptibility and no major alteration in in vivo susceptibility compared with its isogenic nonmucoid parent strain.

Antimicrob Agents Chemother, 1989 Aug, 33(8), 1202 - 6
Decreased outer membrane permeability in imipenem-resistant mutants of Pseudomonas aeruginosa; Trias J et al.; The outer membrane of imipenem-resistant mutants of Pseudomonas aeruginosa was shown to have decreased permeability to imipenem but not to cephaloridine . These experiments were performed with intact cells and liposomes containing imipenem-hydrolyzing beta-lactamase derived from Pseudomonas maltophilia, in both cases utilizing an imipenem concentration of 50 microM . In contrast, liposome swelling assays using imipenem at 8 mM detected no significant difference between the imipenem-resistant mutants and their parents . It was found that the outer membrane of P . aeruginosa has a saturable specific channel through which imipenem travels mainly at low concentrations, whereas at high concentrations this pathway is obscured by diffusion through nonspecific porin channels.

Kansenshogaku Zasshi, 1989 Aug, 63(8), 880 - 5
{Pseudomonas aeruginosa bacteremia associated with hematologic disorders {III} . Prognostic factors}; Funada H et al.; We reviewed 57 episodes of Pseudomonas aeruginosa bacteremia in 55 patients with hematologic disorders such as acute leukemia during a 16-year period, focusing especially on the prognosis . Survival at one week after onset was observed in only 39% of the episodes . Prognosis was significantly better in patients with unimicrobial bacteremia than in those with polymicrobial bacteremia (21/42 vs 1/15, p less than 0.01), in patients without shock than in those with shock (13/21 vs 9/36, p less than 0.02), in patients with granulocyte count at onset of at least 100/mm3 than in those with more marked granulocytopenia (10/13 vs 12/44, p less than 0.01), in patients with an increase in granulocyte count by at least 100/mm3 during their infection than in those without any subsequent increase (18/18 vs 4/13, p less than 0.001), and in patients with total serum protein level at onset of at least 6.0 g/dl than in those with hypoproteinemia (18/32 vs 4/25, p less than 0.01) . Patients with bacteremia secondary to urogenital infection tended to have a higher one-week survival rate than those with pneumonia followed by bacteremia (4/8, 50% vs 2/9, 22%) . With regard to the antibiotic treatment of unimicrobial bacteremia, 14 (70%) of 20 patients receiving therapy with one or two anti-pseudomonal beta-lactam antibiotics and an aminoglycoside in combination that were effective in vitro against the infecting organism survived, and so did only seven (32%) of 22 patients receiving therapy with either one in vitro effective beta-lactam or aminoglycoside or inadequate drugs (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Kansenshogaku Zasshi, 1989 Aug, 63(8), 874 - 9
{Pseudomonas aeruginosa bacteremia associated with hematologic disorders {II} . Blood culture isolates and surveillance cultures}; Funada H et al.; We experienced 57 episodes of Pseudomonas aeruginosa bacteremia in 55 patients with hematologic disorders such as acute leukemia over a 16-year period . All the patients were treated on the same hospital ward . A total of 57 blood culture isolates of P . aeruginosa were divided into nine serogroups . Seventy-four percent of the isolates belonged to four serogroups, which became preponderant one after the other . Surveillance throat and/or stool cultures grew the organisms identical to the isolates from the blood at or prior to the onset of bacteremia in 75% of the episodes . Only 11% of the patients had had P . aeruginosa cultured at admission . The acquisition of the organism was closely associated with antibiotic therapy for other presumed or proved infection . On the other hand, 60% of the episodes occurred during the administration of at least one in vitro effective antibiotic . In five episodes, the patients had received an antipseudomonal penicillin and an aminoglycoside in combination, both of which proved effective in vitro against the infecting organism, when bacteremia occurred . In managing P . aeruginosa bacteremia complicating hematologic disorders, it was thus suggested that surveillance cultures should be regularly carried out, and that attention should be drawn to the occurrence of "breakthrough" bacteremia.

Kansenshogaku Zasshi, 1989 Aug, 63(8), 867 - 73
{Pseudomonas aeruginosa bacteremia associated with hematologic disorders {I} . Predisposing factors and clinical manifestations}; Funada H et al.; We experienced 57 episodes of Pseudomonas aeruginosa bacteremia in 55 patients with hematologic disorders in a 16-year period . Ninety-five percent of the patients had hematologic malignancies such as acute leukemia . All but one patient received cytotoxic or immunosuppressive therapy at or prior to the onset of bacteremia . Seventy-seven percent of the episodes occurred during profound granulocytopenia of below 100/mm3 . All the patients acquired their infection in the hospital, and 96% had received antibiotic therapy during the preceding two weeks . Periodontal, anorectal, lower respiratory tract, and urogenital infections were the sources of bacteremia in about three-quarters of the episodes . Periodontal infection tended to progress to cellulitis of the face or the floor of the mouth, often resulting in bacteremia of the unimicrobial type, while anorectal infection predisposed to abscess formation, frequently leading to bacteremia of the polymicrobial type . Cellulitis at onset was seen in 35% of the episodes . Most sites of infection did not become apparent until one to three days after the onset of fever, probably because of depressed inflammatory response associated with severe granulocytopenia . The majority of patients complained of gastrointestinal symptoms such as nausea and vomiting, abdominal pain, diarrhea, and abdominal fullness at the onset of bacteremia . Major complications included bacteremic shock (63%), impaired consciousness (25%), ecthyma gangrenosum or hemorrhagic gangrenous cellulitis (18%), and jaundice (12%) . Furthermore, there were one case each of endocarditis and disseminated intravascular coagulation . It was thus suggested that the clinical picture of P . aeruginosa bacteremia complicating hematologic disorders is influenced by the predisposing conditions associated with the underlying diseases and their treatment.

Appl Environ Microbiol, 1989 Aug, 55(8), 2036 - 40
Mechanism of resistance to benzalkonium chloride by Pseudomonas aeruginosa; Sakagami Y et al.; The mechanisms of resistance of Pseudomonas aeruginosa to benzalkonium chloride (BC) were studied . The effluence of cell components was observed in susceptible P . aeruginosa by electron microscopy, but resistant P . aeruginosa seemed to be undamaged . No marked changes in cell surface potential between Escherichia coli NIHJC-2 and a spheroplast strain were found . The contents of phospholipids (PL) and fatty and neutral lipids (FNL) in the cell walls of resistant P . aeruginosa were higher than those in the cell walls of susceptible P . aeruginosa . The amounts of BC adsorbed to PL and FNL of cell walls of BC-resistant P . aeruginosa were lower than those for BC-susceptible P . aeruginosa . Fifteen species of cellular fatty acids were identified by capillary gas chromatography and gas chromatography-mass spectrometry . The ability of BC to permeate the cell wall was reduced because of the increase in cellular fatty acids . These results suggested that the resistance of P . aeruginosa to BC is mainly a result of increased in the contents of PL and FNL . In resistant P . aeruginosa, the decrease in the amount of BC adsorbed is likely to be the result of increases in the contents of PL and FNL.

Appl Environ Microbiol, 1989 Aug, 55(8), 1911 - 5
In vivo standardization of cutaneous bactericidal activity of antiseptics by using monoxenic hairless mice; Barc MC et al.; This study was designed to investigate the bactericidal activities of antiseptics on the cutaneous flora of hairless mice monoxenic to Staphylococcus epidermidis, Staphylococcus aureus, or Pseudomonas aeruginosa in vivo . A standardized method for testing such antiseptics to compare their bactericidal effectiveness in humans in described . Seven antiseptics belonging to seven different chemical groups (iodine derivatives, alcohols, mercury compounds, quaternary ammonium salts, biguanides, phenols, and carbanilides) were used as recommended by the manufacturers (conditions of contact or prolonged contact time followed by washing with distilled water) . Germfree hairless mice were infected with various bacterial strains by gastric intubation, producing levels of about 10(3) CFU/cm2 of skin . The antiseptic under test was placed on the right or left side of the ventral region . The contralateral side served as a control . In order to standardize the method, a number of crucial parameters were carefully controlled: the amount of antiseptic applied, the area of skin treated, the duration of treatment, and the washing procedure . Skin samples were obtained by cutaneous biopsy, which effectively removed all the bacteria along with the sample . The bacterial populations were counted before and after application of the antiseptic . Reductions of between 0.5 and 1.9 log units were obtained; these are comparable to those observed in humans . The standardization of our procedure and the use of animals with a strictly controlled flora eliminated much of the variability and sources of error inherent in human studies . This model could be of value for the study of resistant bacterial strains responsible for nosocomial infections and for investigations of damaged skin.

Appl Environ Microbiol, 1989 Aug, 55(8), 1865 - 9
Production of extracellular nucleic acids by genetically altered bacteria in aquatic-environment microcosms; Paul JH et al.; The factors which affect the production of extracellular DNA by genetically altered strains of Escherichia coli, Pseudomonas aeruginosa, Pseudomonas cepacia, and Bradyrhizobium japonicum in aquatic environments were investigated . Cellular nucleic acids were labeled in vivo by incubation with {3H}thymidine or {3H}adenine, and production of extracellular DNA in marine waters, artificial seawater, or minimal salts media was determined by detecting radiolabeled macromolecules in incubation filtrates . The presence or absence of the ambient microbial community had little effect on the production of extracellular DNA . Three of four organisms produced the greatest amounts of extracellular nucleic acids when incubated in low-salinity media (2% artificial seawater) rather than high-salinity media (10 to 50% artificial seawater) . The greatest production of extracellular nucleic acids by P . cepacia occurred at pH 7 and 37 degrees C, suggesting that extracellular-DNA production may be a normal physiologic function of the cell . Incubation of labeled P . cepacia cells in water from Bimini Harbor, Bahamas, resulted in labeling of macromolecules of the ambient microbial population . Collectively these results indicate that (i) extracellular-DNA production by genetically altered bacteria released into aquatic environments is more strongly influenced by physiochemical factors than biotic factors, (ii) extracellular-DNA production rates are usually greater for organisms released in freshwater than marine environments, and (iii) ambient microbial populations can readily utilize materials released by these organisms.

Arch Phys Med Rehabil, 1989 Aug, 70(8), 628 - 31
Chloramine-T solutions: effect on wound healing in guinea pigs; Henderson JD Jr et al.; An evaluation of the wound-healing and disinfectant activities of chloramine-T (Chlorazene) used in hydrotherapy whirlpools was studied in a guinea pig cutaneous wound model . Standard microbiologic methods were used to determine the bacteriocidal activity of Chlorazene in cultures containing up to 2.03 x 10(6) colony-forming units per milliliter of Pseudomonas aeruginosa . Full-thickness skin wounds in 40 guinea pigs were inoculated with Pseudomonas aeruginosa and all animals allowed to recover from anesthesia . Twenty-four hours later, animals were placed in water only or water containing Chlorazene (300ppm) for 20 minutes . This procedure was repeated daily for up to seven days after inoculation of wounded skin . Rate of wound epithelialization and number of infected wounds were determined . Large reductions in numbers of cultured organisms were observed after treatment with Chlorazene . No differences in rate of wound healing could be determined in water- or Chlorazene-treated animals . Chlorazene-treated wounds contained fewer pseudomonas organisms than water-treated controls on postinoculation days five and six . These results confirm that Chlorazene is an effective water disinfectant . Data also indicate that in the concentration used, Chlorazene does not affect the rate of wound healing.

Virology, 1989 Aug, 171(2), 444 - 52
Dual importance of positive charge in the C-terminal region of filamentous bacteriophage coat protein for membrane insertion and DNA-protein interaction in virus assembly; Greenwood J et al.; Gene VIII encoding the procoat protein of the Class II filamentous bacteriophage Pf1 (infecting Pseudomonas aeruginosa) has been cloned and expressed in Escherichia coli and subjected to site-directed mutagenesis . The two positively charged residues clustered near the C-terminus, arginine-44 and lysine-45, were systematically converted to uncharged residues and serine-41 was converted to an arginine residue . Removal of positive charge in the C-terminal region of the molecule seriously impaired the ability of the procoat molecule to undergo insertion at the E . coli cell inner membrane, as manifested by the diminished processing of the N-terminal leader peptide . The basic amino acids near the C-terminus of the coat protein are also involved in neutralizing the negatively charged viral DNA during virus assembly . However, despite its additional positive charge, the S41R mutant protein was unable to participate in the assembly of Class I bacteriophage fd in E . coli . This dual requirement of positively charged residues in the C-terminal region of the coat protein for membrane processing and insertion and for electrostatic neutralization of the encapsidated DNA poses important constraints on the evolution of filamentous bacteriophages with two different helical symmetries.

Am J Clin Pathol, 1989 Aug, 92(2), 192 - 8
An improved method for determining the microbial inhibitory activity of serum and its application to the study of patients with leukemia; Towns ML et al.; Numerous investigators have demonstrated that derangements in serum transferrin and iron can contribute to susceptibility to infection, but the complexity and imprecision of assays have impeded both research and development of clinical testing in this area . This article describes an automated assay for measuring the microbial inhibitory activity of transferrin in serum and its use in patients with acute myelogenous leukemia (AML) and in normal controls . The assay measured the ability of heat-inactivated serum to inhibit the growth of an antibiotic-resistant strain of Pseudomonas aeruginosa . The serum dilutions were prepared in a special low iron chemically defined broth . An inhibition index, the reciprocal of the serum dilution producing 50% inhibition of bacterial growth when compared with the growth in broth alone, was determined . The results showed the serum from the patients with leukemia had a significantly lower inhibition index than that of controls (16 +/- 11 vs . 35 +/- 13, P less than 0.01) . In addition, they had higher serum iron levels (162 +/- 65 vs . 75 +/- 27, P less than 0.01), lower serum transferrin levels (231 +/- 65 vs . 309 +/- 71, P less than 0.01), and higher percentage saturation of transferrin with iron (59 +/- 21 vs . 20 +/- 8, P less than 0.01) than did controls . Because the assay uses equipment available in many clinical laboratories, it could be developed for routine use as an index of susceptibility to infection in selected patients.

J Bacteriol, 1989 Aug, 171(8), 4342 - 8
Protein secretion in Pseudomonas aeruginosa: molecular cloning and characterization of the xcp-1 gene; Bally M et al.; Pleiotropic mutations (xcp) affecting the secretion of proteins in Pseudomonas aeruginosa have been previously characterized and mapped at three different loci on the chromosome . The xcp-1 gene, which is located at the 0-min region, was isolated from a genomic bank containing DNA from P . aeruginosa PAO1 . The recombinant cosmid pLX25 complemented the xcp::Tn5-751 insertion mutation previously described . The xcp-1 gene was located on pLX25 by mapping the insertion point of transposon Tn5-751 and by deletion and subcloning analysis . The xcp-1 gene was expressed when transcription was initiated from a tac promoter, and a 26,000-dalton protein was identified in Escherichia coli minicells . The Xcp-1 protein was associated with the membrane fraction of E . coli . A 30-kilodalton outer membrane protein was also affected by the xcp::Tn5-751 mutation in P . aeruginosa . The possible correlation between Xcp-1 and this protein is discussed.

J Bacteriol, 1989 Aug, 171(8), 4130 - 7
Pseudomonas aeruginosa outer membrane lipoprotein I gene: molecular cloning, sequence, and expression in Escherichia coli; Duchene M et al.; Lipoprotein I (OprI) is one of the major proteins of the outer membrane of Pseudomonas aeruginosa . Like porin protein F (OprF), it is a vaccine candidate because it antigenically cross-reacts with all serotype strains of the International Antigenic Typing Scheme . Since lipoprotein I was expressed in Escherichia coli under the control of its own promoter, we were able to isolate the gene by screening a lambda EMBL3 phage library with a mouse monoclonal antibody directed against lipoprotein I . The monocistronic OprI mRNA encodes a precursor protein of 83 amino acid residues including a signal peptide of 19 residues . The mature protein has a molecular weight of 6,950, not including bound glycerol and lipid . Although the amino acid sequences of protein I of P . aeruginosa and Braun's lipoprotein of E . coli differ considerably (only 30.1% identical amino acid residues), peptidoglycan in E . coli, are identical . Using lipoprotein I expressed in E . coli, it can now be tested whether this protein alone, without P . aeruginosa lipopolysaccharide contaminations, has a protective effect against P . aeruginosa infections.

Phys Ther, 1989 Aug, 69(8), 651 - 5
Inhibition of bacterial growth in vitro following stimulation with high voltage, monophasic, pulsed current; Kincaid CB et al.; Low-intensity direct current has been reported to be effective in promoting healing of infected wounds, and these results have been assumed to apply to stimulation of wound tissue with monophasic high voltage pulsed current (HVPC) . The purpose of this study was to determine whether HVPC has an inhibitory effect on growth in vitro of three bacterial species--Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa--commonly isolated from open wounds . Following exposure to HVPC, the measured zone of inhibition of bacterial growth was not significantly different between bacterial species . Inhibition at the anode (positive pole) occurred secondary to build-up of toxic end products, and inhibition at the cathode (negative pole) resulted from exposure to HVPC . Duration of exposure and voltage showed a highly significant linear relationship . Exposure to more than 250 V of HVPC for at least two hours resulted in some degree of inhibition of growth in all three bacterial species.

Surgery, 1989 Aug, 106(2), 452 - 5; discussion 455-6
The beneficial effect of granulocyte colony-stimulating factor (G-CSF) in combination with gentamicin on survival after Pseudomonas burn wound infection; Silver GM et al.; Inadequate granulopoiesis and decreased granulocyte function are thought to play a significant role in the burned victim's susceptibility to infection . In an attempt to determine whether the regulatory granulopoietic growth factor G-CSF could favorably affect survival when used in combination with antibiotics, we examined survival in a murine model of Pseudomonas aeruginosa burn wound infection . One hundred twenty male BDF1 mice received a 15% total body surface area burn and were randomized to one of five treatment groups: (1) burn only, (2) burn + infection, (3) burn + infection + G-CSF, (4) burn + infection + gentamicin, and (5) burn + infection + G-CSF + gentamicin . Infected mice received a 10(3) colony-forming units topical inoculum of Pseudomonas to the wound immediately postburn . Gentamicin animals received 6.0 mg/kg intraperitoneal gentamicin as a single dose immediately postburn . G-CSF was administered as 100 ng twice daily for 7 days . All treatment groups showed improved survival compared with the burn + infection group, which showed 100% mortality by day 9 (p less than 0.001 all groups; Cox-Mantel statistic) . Group 5 (burn + infection + G-CSF + gentamicin) exhibited improved survival as compared with either group 3 (burn + infection + G-CSF, p = 0.054) or group 4 (burn + infection + gentamicin, p = 0.007) . The use of hematopoietic growth stimulants in combination with antibiotic therapy may result in improved outcome after burn injury, and it suggests new treatment options in the management of postburn infectious complications.

J Biol Chem, 1989 Jul 25, 264(21), 12385 - 8
Histidine 21 is at the NAD+ binding site of diphtheria toxin; Papini E et al.; Treatment of fragment A chain of diphtheria toxin (DT-A) with diethylpyrocarbonate modifies His-21, the single histidine residue present in the chain, without alteration of other residues . Parallel to histidine modification, NAD+ binding and the NAD-glycohydrolase and ADP-ribosyltransferase activities of DT-A are lost . Both NAD+ and adenosine are very effective in protecting DT-A from histidine modification and in preserving its biological properties, while adenine is ineffective . Reversal of histidine modification with hydroxylamine restores both NAD+ binding and enzymatic activities of the toxin . The possible role of His-21 in the activity of diphtheria toxin is discussed in relation to the available three-dimensional structure of the related toxin produced by Pseudomonas aeruginosa.

Ugeskr Laeger, 1989 Jul 24, 151(30), 1934 - 7
{Accumulated microbiological data . Surveillance of infection/antibiotic policy}; Moller JK et al.; Database reviews of the findings in bacteriological specimens from a period of six years from patients in a department of haematology are employed as a model of how cumulative data about the microorganisms isolated may be employed for surveillance of accumulated infections and in the organization of the antibiotic policy of a department . During the period of observation, the standard treatment with antibiotics for febrile episodes in granulocytopenic patients was altered to piperacillin and netilimicin on the basis of the frequent occurrence of Gram-negative rods including Pseudomonas aeruginosa in blood cultures . It is concluded that accumulated microbiological data is of value for a clinical department and that analysis of the data does not constitute an increased work-load provided that the microbiological reports are routinely registered in a database.

Biochim Biophys Acta, 1989 Jul 21, 992(1), 96 - 105
Evidence for the in vivo degradation of human respiratory mucins during Pseudomonas aeruginosa infection; Houdret N et al.; The comparison of distribution of glycopeptides of sputa from patients suffering from various chronic hypersecretions has already shown an increased acidity with a decreased proportion of neutral glycopeptides in the respiratory secretions of patients suffering from cystic fibrosis, as compared to those of patients with chronic bronchitis . In order to find out whether this decrease is specific to cystic fibrosis mucins or whether it is due to a degradation of mucus by Pseudomonas aeruginosa, which infects most of the sputa from patients with this disease, mucus glycopeptides from patients with different chronic bronchial disorders, infected by Pseudomonas or not, were prepared and fractionated by ion-exchange chromatography . The neutral fraction, which has never been studied in detail, was gel-filtered, and provided two fractions, one containing true mucin glycopeptides and the other containing a mixture of peptides and glycopeptides with a lower molecular mass . In the Pseudomonas-infected samples, the true mucin glycopeptide fraction was greatly diminished as compared to this same fraction in non-Pseudomonas-infected samples; this was not specific to cystic fibrosis secretions . In contrast, the glycopeptide fraction with a lower molecular mass was greatly increased in all the Pseudomonas-infected samples . Polyacrylamide gel electrophoresis of this second fraction showed unique glycopeptide bands between 40-50 kDa in the Pseudomonas-infected samples, regardless of the origin of the samples . These bands were revealed by an antibody directed against whole cystic fibrosis mucin . Infected chronic bronchitis sputa and cystic fibrosis samples without P . aeruginosa did not show these bands . These studies therefore suggest that there are P . aeruginosa-associated changes in mucins which may result from degradation of mucins.

Indian J Pathol Microbiol, 1989 Jul, 32(3), 207 - 12
In vitro comparative activity of kanamycin, gentamicin and sisomicin--a new aminoglycoside, against clinical isolates; Lakshmi N et al.; 540 strains of bacteria isolated from various clinical materials comprising 440 strains of Gram negative bacilli and 100 strains of Gram positive cocci were tested for their susceptibility in vitro to Kanamycin, Gentamicin and a new aminoglycoside antibiotic Sisomicin (Ensamycin) . The sensitivity pattern revealed that 68.88% of the strains were sensitive to Kanamycin, 82.9% to Gentamicin and 89.0% to Sisomicin . The effectiveness of Sisomicin is comparatively greater (6.1%) than the other two aminoglycosides . In particular a considerable number of Gentamicin resistant Pseudomonas aeruginosa (12.3%) were found to be sensitive to Sisomicin which is a highly desirable property . Existence of about 11% Sisomium resistant strains even before the wide usage of this antibiotic is note worthy.

J Med Assoc Thai, 1989 Jul, 72 Suppl 2, 29 - 32
A model for testing antiseptic efficacy: a preliminary study on Betadine and Germidine; Thamlikitkul V et al.; Efficacy of povidone iodine antiseptic, betadine and germidine, was tested against normal skin flora and four pathogenic bacteria namely S . aureus, S . epidermidis, E . coli and Pseudomonas aeruginosa by a new model . The study was performed on the volar surface of forearms of ten patients . First of all, the skin flora was cultured then 10(8) cu/ml of the tested organisms was applied by a cotton swab and left to dry for 1 minute before the culture was repeated . Betadine or germidine was applied over the area previously painted with the organism . The culture was taken 1 to 2 minutes thereafter . The results showed that this model was feasible and convenient . Betadine and germidine are efficacious against normal skin flora and pathogenic bacteria.

J Appl Physiol, 1989 Jul, 67(1), 357 - 65
O2- and pneumonia-induced lung injury . II . Properties of pulmonary surfactant; King RJ et al.; Pulmonary surfactant was isolated from the lavage fluids of animals during the course of exposure to 100% O2, 80% O2, 40% O2, or 80% O2 plus 10(8) Pseudomonas aeruginosa instilled intratracheally and analyzed for its phospholipid composition . After 4-5 days of exposure to 100% O2, disaturated phophatidylcholine (DSPC) decreased to 87% of control, whereas the ratio of phosphatidylglycerol to phosphatidylinositol (PG/PI) was 37% of control . Longer periods of ventilation with 100% O2 resulted in DSPC falling to less than 40% of control . The injury was not reversed by reducing the O2 to 50%; rather, a progressive deterioration ensued . Acute respiratory failure (ARF) induced by 5 days of bacterial infection was very similar to that seen after 5 days of exposure to 100% O2 . Ventilation with 80% O2 for 6 days resulted in smaller changes in DSPC but with differences in PG/PI comparable to those seen with 100% O2 or infection . We conclude that the ability of the type II cell to synthesize surfactant of normal composition is significantly impaired in these models of ARF . The earliest index of biochemical modification is the substantial change in PG/PI, which may be predictive of early lung injury . Further exacerbation of the injury could result in the reduction of DSPC content, with subsequent changes in lung mechanics and gas exchange.

J Appl Physiol, 1989 Jul, 67(1), 346 - 56
O2- and pneumonia-induced lung injury . I . Pathological and morphometric studies; Coalson JJ et al.; The physiological, morphological, and morphometric findings of several lung injury models in baboons have been compared in the following six study groups: 1) initial injury with oleic acid followed by ventilation with 100% O2, 2) ventilation with 100% O2, 3) ventilation with 80% O2, 4) ventilation with 80% O2 followed by inoculation of Pseudomonas aeruginosa, 5) ventilation with 40% O2, and 6) normal nonventilated room-air-breathing animals . The animals were maintained for 11 days in an intensive care unit . Light microscopically, animals ventilated with 40 and 80% O2 showed mild lung injury, consisting mostly of an increase in alveolar macrophages in peribronchiolar sites and focal alveolar wall widening . The 100% O2-oleic acid, 100% O2, and 80% O2-Pseudomonas-treated baboons showed mixed exudative-reparative diffuse alveolar lesions . Ultrastructurally, the type II cells of these three groups had significantly altered morphology with aberrations of lamellar body configurations . Morphometric findings showed increases in type II and interstitial cells and decreases in type I and endothelial cells in these injured animals . A striking finding was that the physiological, morphological, and morphometric changes of an 80% O2-Pseudomonas insult was as injurious as 100% O2 . This synergistic effect of hyperoxia and infection very likely reflects the most frequent evolution of adult respiratory distress syndrome in patients in intensive care units.

J Appl Physiol, 1989 Jul, 67(1), 316 - 23
Effect of pyocyanin and 1-hydroxyphenazine on in vivo tracheal mucus velocity; Munro NC et al.; Products of the bacterium Pseudomonas aeruginosa have been shown to slow the beating of human respiratory tract cilia in vitro . We have tested the effects of two of these compounds, pyocyanin and 1-hydroxyphenazine (given as a bolus dose dissolved in 2 microliters Ringer solution), on tracheal mucus velocity of radiolabeled erythrocytes in anesthetized guinea pigs . 1-Hydroxyphenazine (200 ng) caused a rapid slowing of tracheal mucus velocity (maximum fall 47% at 20 min) with recovery by 1 h . The effect of pyocyanin was slower in onset, 600 ng causing 60% reduction in tracheal mucus velocity at 3 h, and no recovery occurred . A combination of pyocyanin and 1-hydroxyphenazine produced an initial rapid slowing equivalent to the same dose of 1-hydroxyphenazine given alone, but the later slowing attributed to pyocyanin was greater than the same dose administered alone . This study demonstrates one mechanism by which products of P . aeruginosa may facilitate its colonization of the respiratory tract.

W V Med J, 1989 Jul, 85(7), 279 - 80
Comparison of in vitro susceptibilities among gram-negative rods; Westblom TU et al.; The activity of mezlocillin, azlocillin and piperacillin was compared using 100 clinical isolates of gram-negative rods . Overall piperacillin had the highest activity with 72 per cent sensitive strains; mezlocillin, 66 per cent, and azlocillin, 57 per cent . In the group of Pseudomonas aeruginosa, however, mezlocillin showed distinctly lower activity than both piperacillin and azlocillin.

Pediatr Med Chir, 1989 Jul-Aug, 11(4), 389 - 91
{Azlocillin in the treatment of pulmonary infections in patients with cystic fibrosis: plasma concentrations and therapeutic indications}; Rosselli P et al.; Azlocillin plasma concentrations have been studied in 10 cystic fibrosis patients suffering from chronic pulmonary infections with Pseudomonas aeruginosa . Patients were given single i.v . doses of 100 e 200 mg/kg body weight as intravenous infusion over 30 minutes . Azlocillin plasma levels have been assayed by a rapid, sensitive and precise high performance liquid chromatographic method . After the dose of 100 mg/kg body weight concentrations of azlocillin decreased below the therapeutic concentrations after three hours; dose of 200 mg/kg was followed by plasma concentrations in the therapeutically desirable range during the 6-8 hours study period . The pharmacokinetic analysis offers further evidence of the dose-dependent nature of azlocillin elimination . Higher dosage of 200 mg/kg body weight and monitoring of plasma drug levels are recommended in the therapy of patients with cystic fibrosis.

Rev Infect Dis, 1989 Jul-Aug, 11 Suppl 5, S1259 - 63
Use of quinolones for the treatment of osteomyelitis and septic arthritis; Waldvogel FA; The low minimal inhibitory concentrations and minimal bactericidal concentrations of the quinolones for most pathogenic gram-negative and many gram-positive organisms, the ease of their administration, and their good oral absorption make them good candidates for the treatment of chronic bone infections . Data presently available suggest that the quinolones are effective in the treatment of experimental osteomyelitis due to Pseudomonas aeruginosa, osteomyelitis due to other gram-negative organisms, and (when combined with rifampin) in the treatment of gram-positive osteomyelitides . Quinolones have also been shown to be effective in the treatment of experimental septic arthritis . These results were confirmed by clinical studies . Quinolones have been effective in the treatment of patients with gram-negative bacterial bone infections and have been as effective as conventional antistaphylococcal therapy in the treatment of osteomyelitis due to Staphylococcus aureus . Finally, it should be kept in mind that as yet quinolones have not been released for use as therapy for childhood infections.

Rev Infect Dis, 1989 Jul-Aug, 11 Suppl 5, S1245 - 52
Use of the new quinolones in cystic fibrosis; Grenier B; Monotherapy with pefloxacin, ofloxacin, or ciprofloxacin for acute exacerbations of bronchopulmonary infection in patients with cystic fibrosis has been shown to be as efficient as traditional intravenous therapy with beta-lactams and aminoglycosides, but these quinolones did not eliminate colonization with Pseudomonas aeruginosa . The only pharmacokinetic parameters that were consistently distinct in patients with cystic fibrosis vs . normal subjects were a higher maximal concentration of drug in serum and a smaller apparent volume of distribution in patients with cystic fibrosis, a finding that is likely related to a reduced cell mass in cachectic patients . Emergence of resistant strains of P . aeruginosa, with cross-resistance to other fluoroquinolones, has been a fairly common event during the course of therapy . Overall tolerance to the quinolones has been satisfactory . No toxic effect was observed in cartilage during or after therapeutic courses in young children . Consequently, it is urged that indications for the use of fluoroquinolones be broadened to include preadolescent patients.

Laryngorhinootologie, 1989 Jul, 68(7), 401 - 6
{Personal studies on the current spectrum of pathogenic bacteria in otitis externa and chronic otitis media}; Feidt H et al.; From 1985-1987 smears (for Gram staining) and swabs (for culture and antibiogram) were done in 294 patients suffering from chronic otitis media, and in 67 cases of external otitis . Besides the comparison of these two procedures, the microbial spectrum in case of external otitis and chronic otitis media is considered and compared to the literature . Pseudomonas aeruginosa and Staphylococcus aureus are the most frequent pathogens . Often gram-positive rod-shaped bacilli were also found, the pathogenicity of which has been underestimated in the literature up to now . The anaerobes did not play an important role in our patients . The value of gram staining (immediate information and safer antibiotic therapy) is pointed out on the basis of the reported results.

Acta Anaesthesiol Scand, 1989 Jul, 33(5), 379 - 84
Cortisol deficiency in metomidate anesthetized bacteremic pigs: results in circulatory failure--beneficial effect of cortisol substitution; Neumann R et al.; Etomidate and the closely related metomidate are known to inhibit cortisol synthesis . We studied the influence of metomidate on hemodynamic performance and survival time of bacteremic pigs . Thirty pigs, 30.2 +/- 0.8 kg, were anesthetized with intravenous metomidate (2.5 mg.kg-1.h-1) plus ketamine (3.0 mg.kg-1.h-1), and were then mechanically ventilated . The animals were randomly allocated to three groups of 10 pigs each . Group A received an infusion of live Pseudomonas aeruginosa bacteria (2.5.10(9).kg-1.h-1 organisms until death), Group B additionally received a bolus of 1 mg.kg-1 cortisol (followed by an infusion of 0.1 mg.kg-1.h-1) starting 1 h prior to the bacterial infusion, and Group C served as anesthesia control without receiving bacteria or cortisol . The experiments in Group C were terminated after 10 h . In Group A the cortisol level was severely suppressed from the very beginning . The animals died of circulatory failure after 4.3 +/- 0.4 h . In contrast, Group B exhibited fairly stable hemodynamics, but the animals died due to pulmonary edema after 11.1 +/- 1.3 h . Cortisol deficiency in metomidate anesthetized pigs facilitates the development of circulatory failure in the course of Pseudomonas bacteremia, which does not occur if cortisol is infused to reconstitute a physiological level . However, this cortisol substitution did not prevent the development of pulmonary edema caused by Pseudomonas aeruginosa . Possible mechanisms of the deleterious effect of cortisol deficiency and implications in regard to the clinical use of metomidate/etomidate are discussed.

Rev Infect Dis, 1989 Jul-Aug, 11 Suppl 5, S960 - 8
Bacterial resistance to quinolones: mechanisms and clinical importance; Wolfson JS et al.; An overview of bacterial resistance to new quinolones is presented with a consideration of mechanisms, clinical importance, and approaches to suppression of the emergence of resistance . Single-step mutation to high-level resistance occurs at a frequency of less than or equal to 10(-10) for many bacterial species but can be readily selected by serial exposure of cells to increasing drug concentrations . Two mechanisms of resistance have been identified: alteration in the target enzyme DNA gyrase and decreased drug permeation . Emergence of resistance to clinically useful quinolones thus far has been uncommon . Superinfection has been documented but also has been uncommon . Emergence of resistance appears to occur more often with certain bacterial species, including Pseudomonas aeruginosa and Staphylococcus aureus . In the special setting of cystic fibrosis, patients with P . aeruginosa infections often respond favorably despite emergence of resistance . Methods to minimize the emergence of quinolone resistance should be evaluated in an effort to preserve the clinical utility of these drugs.

J Bacteriol, 1989 Jul, 171(7), 3917 - 25
In vivo cloning of Pseudomonas aeruginosa genes with mini-D3112 transposable bacteriophage; Darzins A et al.; The transposition properties of the Pseudomonas aeruginosa mutator bacteriophage D3112 were exploited to develop an in vivo cloning system . Mini-D replicon derivatives of D3112 were constructed by incorporating broad host range plasmid replicons between short terminal D3112 sequences . These elements were made with small replication regions from the RK2, Sa, and pVS1 plasmids and selectable genes for tetracycline, carbenicillin, kanamycin, and gentamicin resistance . Some of the mini-D replicons also contain the RK2 oriT origin-of-transfer sequence, which allows them to be mobilized by conjugation to many different species of gram-negative bacteria . These elements were used to clone DNA by preparing lysates from P . aeruginosa cells harboring an inducible D3112 cts prophage and a mini-D replicon plasmid . These lysates were used to infect sensitive P . aeruginosa recipients and select recombinant plasmids as drug-resistant transductant colonies . These transductants form a gene library from which particular clones can be selected, such as by their ability to complement specific mutations . This system was used to clone nine different genes from the PAO chromosome . The ability of this system to precisely identify a gene was demonstrated by isolating clones of the argF+ and cys-59+ genes . Restriction maps of clones of these genes, which have different amounts of flanking DNA, located the positions of these genes . The sizes of the chromosomal DNA segments from 10 individual clones examined ranged from 6 to 21 kilobases (kb), with an average of about 10 kb . This is consistent with the approximately 40-kb DNA-packaging size of the D3112 phage.

J Bacteriol, 1989 Jul, 171(7), 3909 - 16
Mini-D3112 bacteriophage transposable elements for genetic analysis of Pseudomonas aeruginosa; Darzins A et al.; Small bacteriophage D3112 transposable elements deleted for most of the phage-lytic functions while retaining the sites required for transposition and packaging were constructed to facilitate genetic studies in Pseudomonas aeruginosa . These mini-D derivatives were constructed with the terminal 1.85 kilobases (kb) of the phage left end and 1.4 kb of the phage right end and either the Tn5 kanamycin resistance or the pSC101 (pBR322) tetracycline resistance determinant . Thermally induced lysates of strains lysogenic for both a mini-D element and D3112 cts (temperature-sensitive repressor) transduced P . aeruginosa PAO recipients to drug resistance at frequencies of between 10(-4) and 10(-5)/PFU of the helper phage . As for the parent plaque-forming D3112 phage, the mini-D171 element could insert itself into many different sites in the chromosome but the frequency of insertion into particular genes varied widely . Among 1,000 insertions, none resulted in auxotrophy but 10 resulted in pigment production . Insertions were also selected in a cloning plasmid with a transduction scheme . At least eight different insertion sites were found to have been used among 10 individual insertions . Transductants harboring these mini-D elements were immune to infection by D3112, since they contained the D3112 repressor gene in the left 1.85-kb terminal fragment . Chromosomal genes were transduced in a generalized fashion 100 to 1,000 times more frequently by the mini-D-D3112 cts lysates than by the D3112 cts phage alone . Mini-D171-D3112 cts lysates also yielded some transductants that retained the drug resistance marker of the mini-D element and which were unstable for the chromosomal transduced marker . This is consistent with the miniduction properties of Mu whereby transduced genes are flanked by two mini-D elements in the same orientation.

J Bacteriol, 1989 Jul, 171(7), 3680 - 8
Control of mucoidy in Pseudomonas aeruginosa: transcriptional regulation of algR and identification of the second regulatory gene, algQ; Deretic V et al.; A new alginate regulatory gene, algQ, was identified in a chromosomal region which, when tandemly amplified, induces mucoidy in Pseudomonas aeruginosa . The algQ gene was found closely linked to the previously identified algR gene . Both algQ and algR were required for transcription of the key alginate biosynthetic gene, algD . In addition, expression of the algR gene was studied . The algR promoter was mapped by S1 nuclease and reverse transcription and found to be activated in mucoid cells . However, even in nonmucoid cells, transcription of algR was detectable at an approximately 50-fold-lower level, as opposed to the algD promoter, which was silent in the nonmucoid background . Transcription of both promoters was studied by using algR- and algD-specific oligonucleotides and total cellular RNA from fresh cystic fibrosis isolates of mucoid P . aeruginosa and their nonmucoid revertants . Identical patterns of activity were found in all strains: in mucoid cells, both algR and algD were activated . This finding indicated that common mechanisms were involved in the regulation of alginate gene expression . However, when the algR gene was cloned behind the tac promoter on a broad-host-range-controlled expression vector, induction of transcription with isopropropyl-beta-D-thiogalactopyranoside (IPTG) caused the appearance of a nonmucoid phenotype in previously mucoid cells . This effect was transient, since removal of the inducer (IPTG) made cells mucoid again . Since the algR gene product is homologous to transcriptional regulators from a class of environmentally responsive systems (known to have a second, sensory component), the algQ gene could be a candidate for the sensory component of the alginate system.

J Clin Immunol, 1989 Jul, 9(4), 287 - 95
Functional immunoregulatory T-cell abnormalities in cystic fibrosis patients; Lahat N et al.; The role of B cells and regulatory T cells in the reduced in vitro IgG synthesis of cystic fibrosis (CF) patients was studied . Intact proportion, proliferation, and differentiation of B cells and reduced suppressor and helper T-cell function were found . To explore the T-cell defects further, CF sera or supernatant derived from Pseudomonas aeruginosa cultures (PA supernatant) was added to the relevant T helper- and suppressor-cell assays . Both CF sera derived from PA-positive patients and PA supernatant interfered with the appearance of interleukin 2 (IL-2) receptors and with the functional enhancement caused by exogenously added IL-2 . PA-negative CF patients, however, also had functional T-cell defects and inhibitory sera, but these sera did not affect IL-2 pathways . Thus different serum factors and intrinsic T-cell defects in CF patients are suggested.

Arch Roum Pathol Exp Microbiol, 1989 Jul-Sep, 48(3), 193 - 207
Comparative study of the biological characteristics of mucoid and non-mucoid Pseudomonas aeruginosa strains isolated from chronic respiratory infections; Meitert E et al.; Morphological, culture and enzymatic characteristics, as well as virulence, susceptibility to antimicrobial agents and epidemiological markers, were studied for 100 mucoid and 100 non-mucoid Ps . aeruginosa strains isolated from chronic respiratory infections . For 10 mucoid and 10 non-mucoid strains was performed the active protection test in mice, both with inactivated germs (10(9) germs), and LPS extracted by Westphal method . It was ascertained that mucoid Ps . aeruginosa strains differ from non-mucoid strains by the slow growth on culture media, more reduced proteolytic activity (81% as compared to 99%), slow oxidation of carbohydrates (5-7 days), reduced virulence in mice (8%) or avirulence (92%), higher sensitivity to some antibiotics (amikacin, dibekacin, ticarcillin, tetracycline, cefotaxime, ceftriaxone), lysoresistance (74%) and polyagglutinability (67%) . The mucoid strains ensure a reduced active protection in mice, 70% of strains did not protect the mice against the infection with virulent homologous strains, while the non-mucoid strains ensured 80%-100% protection.

Rev Argent Microbiol, 1989 Jul-Dec, 21(3-4), 149 - 52
{Presence of extracellular proteases in Pseudomonas aeruginosa}; Pajaro MC et al.; Proteolytic activity on hide power azure (HPA) and elastin was assayed in 32 Pseudomonas strains . Dye substrates were incubated with culture supernatants for 30 min at 37 degrees C and then released dye was measured photocolometrically . 100% of strains showed proteolytic activity on HPA and 56.25% were elastase positive, the values obtained with the first substrate were the highest . No relation with strain origin was established.

Arch Dis Child, 1989 Jul, 64(7), 1022 - 8
Treatment of pseudomonas aeruginosa colonisation in cystic fibrosis; Steinkamp G et al.; To test whether early treatment could postpone the chronic colonisation of the respiratory tract with mucoid strains of Pseudomonas aeruginosa in patients with cystic fibrosis, we performed a pilot study in 28 patients aged 2 to 18 years . A two week course of azlocillin (150 mg/kg/day) and tobramycin (10 to 15 mg/kg/day) was given after a mean duration of P aeruginosa colonisation of five months (range one to 11 months) . Weight for height increased significantly by 3.5% (SEM 0.7%) of the predicted normal after chemotherapy . The eradication of P aeruginosa that was achieved in 18 children directly after hospital treatment was only temporary . Samples from only 10 and five patients remained negative three and six months after treatment, respectively . Five children remained free from P aeruginosa for a prolonged period of 14 to 32 months . We conclude that, apart from the clinical improvement in all patients, some children might benefit from early antipseudomonas treatment with respect to the bacteriological outcome . Most children, however, experience only a temporary reduction in colonisation . Further investigations in form of controlled clinical trials seem justified.

Am J Respir Cell Mol Biol, 1989 Jul, 1(1), 37 - 9
Nonchromogenic hydrolysis of elastase and cathepsin G p-nitroanilide substrates by Pseudomonas aeruginosa elastase; Pelletier A et al.; Pseudomonas aeruginosa, which may cause severe lung infections, secretes a metalloelastase that may interfere with the assay of neutrophil elastase and cathepsin G in lung secretions . Using nuclear magnetic resonance spectroscopy, we have shown that P . aeruginosa elastase (PsE) cleaves succinyl-Ala3-p-nitroanilide between the first and the second alanine residue, rendering this substrate inefficient for the assay of neutrophil elastase . The cleavage occurs with a kcat/Km of 2.4 X 10(3) M-1 s-1, a value eightfold higher than the kcat/Km for the chromogenic cleavage of succinyl-Ala3-p-nitroanilide by neutrophil elastase . P . aeruginosa elastase also cleaves the elastase substrate succinyl-Ala3-Val-p-nitroanilide between the second and the third alanine residue and the cathepsin G substrate succinyl-Ala2-Pro-Phe-p-nitroanilide at the Pro-Phe linkage . By contrast, methoxysuccinyl-Ala2-Pro-Val-p-nitroanilide, another elastase substrate, is not hydrolyzed by the bacterial enzyme . Our data indicate that synthetic substrates should be used with caution to assay elastase and cathepsin G in lung secretions or other biologic fluids in which metalloproteinases may be present.

Mikrobiologiia, 1989 Jul-Aug, 58(4), 607 - 10
{Degradation of alkylsulfates by a Pseudomonas aeruginosa culture immobilized on a polyvinyl alcohol fiber}; Stavskaia SS et al.; Pseudomonas aeruginosa cells capable of destroying alkyl sulfates, anionic surfactants, were immobilised on activated polyvinyl alcohol fibres . The immobilised cells could decompose SDS . When the immobilised cells were used repeatedly, their biomass increased but the activity hardly changed.

Kansenshogaku Zasshi, 1989 Jul, 63(7), 748 - 56
{Study of the prophylactic effect of ubenimex on experimental pyelonephritis induced by Pseudomonas in neutropenic mice}; Tanaka N et al.; We investigated the prophylactic effect of Ubenimex on mice with ascending pyelonephritis induced by Pseudomonas aeruginosa (G-group) . This experimental model was established by a two course administration of cyclophosphamide, so that it kept the mice in a neutropenic status (around 2000 white blood cells/mm3) from the time of infection to the time of sacrifice . The cyclophosphamide-treated group increased their susceptibility more than the control group . In the cyclophosphamide-treated group, the prophylactic administration of Ubenimex (100 micrograms/day/mouse) did not produce significant decreases of infection-induced mortality rate, but yielded a lower incidence of infection than of saline alone . Administration of Ubenimex was not able to increase the number of neutrophils during the experiment . An investigation of the bactericidal capacity of peritoneal exudating neutrophils revealed that Ubenimex prophylactic administration accelerated its capacity, although cyclophosphamide alone did not . These results suggest that Ubenimex has a prophylactic effect on bacterial infection in neutropenic mice, and that this effect, in part, depends upon the acceleration of bactericidal capacity of neutrophils produced by Ubenimex.

J Pharmacobiodyn, 1989 Jul, 12(7), 398 - 404
Production and some properties of monoclonal antibodies against serotype strains of Pseudomonas aeruginosa; Yoshida K et al.; A set of 16 serotype specific monoclonal antibodies (MoAbs) against Pseudomonas aeruginosa classified by Homma were obtained by the mouse hybridoma technique . This set of MoAbs was useful for classification of their serotypes especially O-antigen groups G and M . MoAb obtained from serotype 15 of Homma's classification reacted with serotype 17 of the same classification . We also obtained two MoAbs which reacted with 7 Homma's serotypes of 6 different O-antigen groups and one MoAb which recognized all 4 Homma's serotypes of O-antigen group B . These MoAbs were also useful in mice for the preventive effect against the infections of P . aeruginosa.

Diagn Microbiol Infect Dis, 1989 Jul-Aug, 12(4), 343 - 9
Synergy of new C-3 substituted cephalosporins and tobramycin against Pseudomonas aeruginosa and Pseudomonas cepacia; Chin NX et al.; The effects of the combination of E-1040, a new cephalosporin, ceftazidime, cefpirome, or cefepime with tobramycin against 40 Pseudomonas aeruginosa and 16 P . cepacia isolates from cystic fibrosis patients were examined . Synergy fractional inhibitory concentration less than or equal to 0.5 was found against P . aeruginosa when tobramycin was combined with E-1040 32%, cefpirome 32%, cefepime 22%, and ceftazidime 22% . Fifty-two percent of isolates showed an additive response for E-1040, 60% for cefpirome, 45% cefepime, and 55% ceftazidime, p greater than 0.05 . The differences were not statistically significant . Synergy was not more likely to be achieved if the isolates were susceptible or resistant to either the aminoglycoside or cephalosporin . None of the E-1040-resistant isolates, all of which were tobramycin-resistant, became susceptible when tested with an aminoglycoside, whereas 15 of 34 cefpirome-resistant, 13 of 30 cefepime-resistant, and seven of 14 ceftazidime-resistant isolates became susceptible . Synergy of aminoglycoside and the cephalosporins against P . cepacia was found for 25% with E-1040, 44% with cefpirome, 38% with cefepime, and 31% with ceftazidime . These differences were not statistically significant.

Diagn Microbiol Infect Dis, 1989 Jul-Aug, 12(4), 337 - 41
In vitro comparison of cefpirome and four other beta-lactam antibiotics alone and in combination with tobramycin against clinical isolates of Pseudomonas aeruginosa; Cabezudo I et al.; In vitro susceptibility studies of cefpirome versus cefotaxime, ceftazidime, imipenem, and piperacillin alone and in combination with tobramycin were performed against 153 clinical isolates of Pseudomonas aeruginosa from four medical centers . The minimal inhibitory concentration (MIC) for each antibiotic alone was determined by a standardized dilution method . Antibiotic combination studies were performed using a modified checkerboard technique . Cefpirome alone was more active (MIC90 64 micrograms/ml) than piperacillin (MIC90 128 micrograms/ml) or cefotaxime (MIC90 256 micrograms/ml) but less active than imipenem (MIC90 2 micrograms/ml) or ceftazidime (MIC90 32 micrograms/ml) . The addition of tobramycin reduced the MICs of all of the beta-lactam antibiotics except for imipenem . The MIC90 for cefpirome when combined with tobramycin was 8 micrograms/ml compared to 16 micrograms/ml for cefotaxime and piperacillin, 8 micrograms/ml for ceftazidime, and 4 micrograms/ml for imipenem . The combination of tobramycin and cefpirome proved to be additive or synergistic for 82% of the isolates (highest rate) compared to 31% with imipenem (lowest rate) . The potent in vitro antipseudomonal activity of cefpirome alone and in combination with an aminoglycoside (tobramycin) suggests that this agent may play a useful role in the therapy of infections due to P . aeruginosa.

Zh Mikrobiol Epidemiol Immunobiol, 1989 Jul, (7), 59 - 62
{Experimental vaccinal prophylaxis of Pseudomonas aeruginosa burn sepsis}; Bandman OA et al.; After the injection of P . aeruginosa live culture under the burned skin of mice sepsis develops within the first 24 hours, finally leading to the death of the animals . The microorganisms can be isolated from the blood, liver, kidneys and mesenterial lymph nodes till day 3 and from the spleen till day 5 . After the intraperitoneal injection of P . aeruginosa live culture into mice, sepsis also develops within 24 hours, and the culture can be isolated from the blood and parenchymatous organs till day 3 . The LD50 of the culture is equal to 5.1 X 10(6) microbial cells when introduced intraperitoneally and to 30 microbial cells in experimental burn sepsis . Experimental burn sepsis clearly demonstrates the effectiveness of Pseudomonas acellular protein vaccine: its index of effectiveness exceeds 3,000.

Jpn J Med, 1989 Jul-Aug, 28(4), 503 - 5
A case of diffuse panbronchiolitis (DPB) with benign monoclonal IgA gammopathy and IgA nephropathy with monoclonal IgA deposition; Naito T et al.; A case of diffuse panbronchiolitis (DPB), associated with benign monoclonal IgA gammopathy and IgA nephropathy is described . The IgA deposition in the glomeruli of the patient was identified as consisting mainly of the monoclonal IgA having the same idiotype as that of serum monoclonal IgA . Recurrent infections of Hemophilus influenzae and Pseudomonas aeruginosa in the respiratory tract might have enhanced IgA-mediated immunity at the mucosal surface of the bronchiole, and ultimately induced monoclonal IgA gammopathy and IgA nephropathy.

Genetika, 1989 Jul, 25(7), 1168 - 78
{The effect of the IncP-2-group plasmid on the growth of Pseudomonas aeruginosa bacteriophages}; Freizon EV et al.; The influence of plasmids of the IncP-2 group on development of bacteriophages of Pseudomonas aeruginosa was studied . Six different types of phage growth inhibition conferred by natural plasmids of the IncP-2 group were found . All these plasmids were shown to have no effect on adsorption and injection of phage DNA into cells, only blocking intracellular phage development . The differences between phage inhibition mechanisms were shown by comparison of efficiency of colony formation by cells containing different plasmids, in the presence of different phages . The presence of the RpL11 plasmid reduces the frequency of lysogenization with G101 phage but not with B3 phage . The mutants of pMG53 plasmid having modified phage inhibition spectrum were obtained . It was inferred that inhibition of different phages is under control of different loci of this plasmid . The mutants of phage B3 overcoming inhibition by plasmids were obtained . It was supposed that the plasmids act at least at three different sites of the phage B3 genome.

Vet Med (Praha), 1989 Jul, 34(7), 411 - 9
{Pseudomonas aeruginosa in raw and pasteurized milk}; Mickova V et al.; Eighteen strains of Pseudomonas aeruginosa, i.e . 8.87%, were isolated during a year from 203 samples of raw milk . Two Pseudomonas aeruginosa strains, i.e . 4%, were isolated from 50 samples of pasteurized milk . The strains were isolated using propagation techniques in meat-peptone broth with malachite green and on selective media--on centrimide agar (CEM) and on Pseudomonas F agar . All the isolated strains produced protease, whereas lipase was produced by only five strains . The strains were devitalized when exposed to pasteurization temperatures (72 degrees C) for 20 seconds . At cold store temperatures (4 degrees C), Pseudomonas aeruginosa strain cells propagated on average by two orders, inhibitory effects of low temperatures were recorded only with one strain . Inhibitory effects of milk cultures (cream, yogurt) on Pseudomonas aeruginosa were observed; their effects were more clear-cut at the temperature of 4 degrees C . The strains were markedly susceptible to gentamycin.

Mol Microbiol, 1989 Jul, 3(7), 861 - 8
Pseudomonas aeruginosa cytotoxin: the nucleotide sequence of the gene and the mechanism of activation of the protoxin; Hayashi T et al.; The gene encoding cytotoxin (ctx) was cloned from Pseudomonas aeruginosa 158 and the nucleotide sequence was determined . The structural gene of ctx encodes the procytotoxin of 286 amino acid residues with a molecular mass of 31,681 Daltons . Procytotoxin was activated by removal of 20 amino acid residues from the C terminus with trypsin . The cloned ctx gene was not expressed in either an Escherichia coli strain or a cytotoxin non-producing strain of P . aeruginosa . An expression system for the ctx gene was constructed by placing the structural gene of ctx downstream of tac promoter on a broad host-range vector plasmid.

Arzneimittelforschung, 1989 Jul, 39(7), 750 - 4
Sub-inhibitory and post-antibiotic effects of an optically active isomer of ofloxacin; Tanaka M et al.; The sub-inhibitory and post-antibiotic suppressive effects of DR-3355, an optically active isomer (S-(-) form) of (+/-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methylpiperazin-1-yl)-7- oxo-7H- pyrido{1,2,3-de}-1,4-benzoxazine-6-carboxylic acid (ofloxacin) were compared with those of ofloxacin, ciprofloxacin and ceftazidime by observing changes in bacterial multiplication and morphology in vitro . DR-3355 affected the proliferation of Staphylococcus aureus E46, Escherichia coli E77156 and Pseudomonas aeruginosa PI-III at 1/4 to 1/2 times the minimal inhibitory concentration (MIC) for each strain . The compound also affected the morphology of these strains at 1/32 times the MICs . Upon MIC basis, these sub-inhibitory effects of DR-3355 were almost identical to those of the reference compounds . On the other hand, exposure of E . coli to 1 and 4 times the MIC of DR-3355 for 3 h produced post-antibiotic effects of 0.7 and 1.9 h, respectively, and the effects of the compound were almost equal to those of ofloxacin and ciprofloxacin and much greater than that of ceftazidime.

Microbiologica, 1989 Jul, 12(3), 257 - 61
Role of alkaline protease and elastase in the adherence of Pseudomonas aeruginosa to WEHI cells; Trancassini M et al.; Recent clinical isolates were tested for production of some extracellular factors such as alkaline protease and elastase . They were also assayed for adhesiveness to WEHI cells . It is well known that extracellular production of substances other than toxins is related to virulence and may increase adherence . The present investigation aimed to evaluate the role of extracellular proteins in adherence . Alkaline protease production was assayed using a test performed with casein as substrate while elastase activity was investigated with the elastin-congored method . Our results demonstrated that P . aeruginosa strains which are good alkaline protease and elastase producers adher better than those showing no or low protease and elastase activity.

J Clin Microbiol, 1989 Jul, 27(7), 1650 - 4
L-form-like colonies of Staphylococcus aureus induced by an extracellular lytic enzyme from Pseudomonas aeruginosa; Falcon MA et al.; An extracellular enzyme produced by Pseudomonas aeruginosa had a lytic effect on lyophilized Staphylococcus aureus cells . It was purified from the culture supernatant by ammonium sulfate fractionation followed by column chromatography with P cellulose and Sephadex G-50 . The molecular weight of the enzyme was estimated to be 19,000 +/- 1,750 with sodium dodecyl sulfate-polyacrylamide gel electrophoresis . The pI of the enzyme was estimated to be 8.5 with isoelectric focusing . The enzyme was inactive in 4% NaC1-40 mM sodium phosphate buffer or at pH values lower than 6.0 or higher than 11.0; however, it was not affected by 1 M sucrose or 0.25% heat-denatured horse serum . The action of the enzyme on cultures of S . aureus resulted in the presence of many cells lacking cell walls . In addition, when cultivation was carried out on osmotically stabilized solid media, these cell wall-deficient cell developed in L-form colonies.

Br J Plast Surg, 1989 Jul, 42(4), 380 - 4
Wound sterilization: CO2 laser versus iodine; al-Qattan MM et al.; Control of infection in a surgical wound remains a challenge, especially if further surgery in the area is needed . This study was designed to compare the effectiveness of sterilization of a standard experimental infected wound by surgical skin preparation (Betadine) as compared to treatment with the CO2 laser . Standard wounds (5 x 6 cm) were created superficial to the panniculus carnosus on each flank of 37 adult male New Zealand rabbits . Each wound was infected with a standard dose of Pseudomonas aeruginosa . All wounds became grossly infected . On the third day one flank wound was treated with the CO2 laser, the other with the Betadine solution, and a punch biopsy (4 mm) was taken from each wound for quantitative bacterial counts . Less than 10% of the laser-treated wounds grew Pseudomonas, whereas nearly 40% of the iodine-treated wounds remained infected (P less than 0.005) . Our early clinical experience using the CO2 laser for the sterilization of infected wounds is also reported.

APMIS, 1989 Jul, 97(7), 631 - 6
A comparison of the efficiency in serotyping of Pseudomonas aeruginosa from cystic fibrosis patients using monoclonal and polyclonal antibodies; Ojeniyi B et al.; A well-known problem in serotyping Pseudomonas aeruginosa strains from cystic fibrosis patients using polyclonal sera is that more than half of the strains cannot be assigned to a single O-serogroup because of the high occurrence of polyagglutinable strains and nontypable strains . In the present study, the efficiency of a set of O-specific monoclonal antibodies in the simple slide agglutination test was compared with polyclonal sera for the serotyping of 243 isolates of P . aeruginosa from cystic fibrosis patients . Using the monoclonal antibodies, 213 (88%) strains were found to be typable and only 30 (12%) strains were nontypable . In contrast, when the polyclonal sera from Statens Seruminstitut were used, only 53 (22%) strains were typable . Similar results were obtained when polyclonal sera manufactured by Difco were used where only 61 (25%) strains were typable . We also investigated the consistency of each set of antibodies in typing of the same isolates on different days and found that the polyclonal sera showed higher reproducibility . The Statens Seruminstitut sera were found to have an 86% reproducibility while the Difco sera scored 81%; however, the percentage of strains that are nontypable remains below 25% despite the highly reproducible results obtained . The monoclonal antibodies were found to score a 75% reproducibility when the serotyping of the same strains was done both in the laboratories of Copenhagen and of Guelph . However, it should be noted that although the reproducibility was somewhat lower with the monoclonal antibodies, these highly specific antibodies are still clearly superior when compared with polyclonal sera used because more than 80% of the strains from cystic fibrosis can now be assigned to a single O-serogroup.

Am Rev Respir Dis, 1989 Jul, 140(1), 206 - 10
The pulmonary clearance of smooth and rough strains of Pseudomonas aeruginosa; Martin HG et al.; Upper airway colonization with rough strains of Pseudomonas is associated with clinical deterioration in patients with cystic fibrosis . These rough strains are less toxic than smooth strains in the burned mouse model and in vitro assays . We measured the 4-h pulmonary clearance of 10(4) and 10(6) rough and smooth Pseudomonas after intrabronchial inoculation . After 10(4) Pseudomonas, rough strains were cleared more efficiently than smooth strains (89 +/- 13% versus 140 +/- 19% of the original inoculum, respectively, p less than 0.05) . This was associated with more total bronchoalveolar lavage PMNs after inoculation with rough as compared with smooth Pseudomonas (1.60 +/- 0.38 x 10(5) versus 0.55 +/- 0.09 x 10(5), respectively, p less than 0.05) . After inoculation with 10(6) Pseudomonas, rough were cleared less efficiently than smooth Pseudomonas (380 +/- 45% versus 134 +/- 12% of the original inoculum, respectively, p less than 0.05) . There was no difference in the BAL PMNs of the animals inoculated with either bacterial strain at this inoculum (8.1 +/- 0.6 x 10(5) and 9.4 +/- 1.0 x 10(5) for the rough and smooth Pseudomonas, respectively) . When PMN differences were abolished in C5-deficient mice, 10(4) rough were cleared less efficiently than smooth Pseudomonas . The relatively poor clearance of rough Pseudomonas could not be explained by in vitro differences in PMN killing or BAL toxicity or by intrinsic growth rates.

Infect Immun, 1989 Jul, 57(7), 1873 - 8
Effects of eliminating a disulfide bridge within domain II of Pseudomonas aeruginosa exotoxin A; Madshus IH et al.; Cysteines 265 and 287 of Pseudomonas aeruginosa exotoxin A (ETA) were substituted by serine, thereby eliminating a disulfide bridge within domain II, the putative membrane insertion-translocation domain . Purified mutant toxin was 80-fold less toxic for mouse L cells than was wild-type ETA while retaining the same specific activity in the ADP-ribosyltransferase reaction as did wild-type toxin . Binding of the nonionic detergent Triton X-114 by mutant ETA occurred at a slightly higher pH than did binding by wild-type ETA, suggesting that the mutant protein more readily undergoes a conformational change exposing hydrophobic regions . Data are presented supporting the notion that the mutant and wild-type toxins enter from the same intracellular compartment . The lower cytotoxicity of the mutant protein could be due to accelerated intracellular degradation or abortive, premature membrane insertion.

Kansenshogaku Zasshi, 1989 Jul, 63(7), 738 - 47
{Study of the prophylactic effect of human granulocyte-colony stimulating factor (G-CSF) on experimental pyelonephritis induced by Pseudomonas aeruginosa in diabetic mice}; Yokoo A et al.; The compromised host has recently increased because of the improvement of medical diagnosis and technology . Infection in the compromised host is somewhat different from that in common patients, since this infection is caused by impairment of the host defense mechanism . And the compromised host easily suffers from opportunistic infections . This situation prompted us to study the effect of biological response modifiers (BRMs), which activate the host defense mechanism against infections in the compromised host . We used streptozotocin (STZ)-induced diabetic mice, as experimental models of the compromised host . First, we investigated the bactericidal capacity of the perineal exudating neutrophils in diabetic mice, as one of the host defense mechanism . Second, we also studied the effect of Granulocyte-Colony Stimulating Factor (G-CSF) on diabetic mice with ascending pyelonephritis by P . aeruginosa . At 1 and 2 weeks after inducing the diabetic state, no difference was found in the bactericidal capacity of the perineal exudating neutrophils between normal mice and diabetic mice . At 3 weeks, however, this bactericidal capacity was markedly suppressed in these mice . This result suggested that a depression of host defense mechanisms in diabetics was caused by, in part, a suppression of bactericidal capacity of neutrophils . When G-CSF (2 micrograms/mouse) was injected subcutaneously once a day into diabetic mice, the suppression of the bactericidal capacity of neutrophils significantly recovered . We thus studied the effect of G-CSF on diabetic mice against infection . Diabetic mice increased their susceptibility to bacterial infection more than normal mice . In diabetic mice, administration of G-CSF (2 micrograms/mouse) yielded a lower incidence of infection and infection-induced mortality than those of controls . These data show that G-CSF may be of great value for prevention and treatment of opportunistic infections in the compromised host, especially in patients whose bactericidal capacity of neutrophils is depressed, as in diabetics.

Infect Immun, 1989 Jul, 57(7), 2187 - 95
Induction of inflammatory mediators (histamine and leukotrienes) from rat peritoneal mast cells and human granulocytes by Pseudomonas aeruginosa strains from burn patients; Bergmann U et al.; Clinical isolates of Pseudomonas aeruginosa from severely burned patients were analyzed with regard to their capacity to induce inflammatory-mediator release from rat mast cells or human granulocytes . The bacterial strains were characterized according to their cell-associated hemolysin activity as well as their secreted hemolysin and phospholipase C activities . P . aeruginosa expressing heat-labile hemolysin and phospholipase C induced histamine release from rat mast cells and leukotriene formation from human granulocytes, while bacterial strains expressing heat-stable hemolysin were potent releasers of histamine but did not lead to leukotriene formation . The mediator-inducing capacity was dependent on the growth characteristics of the bacterial strains . The purified glycolipid (heat-stable hemolysin) of P . aeruginosa was a potent inducer of histamine release but did not initiate leukotriene formation . Exotoxin A did not affect inflammatory-mediator release . P . aeruginosa with leukotriene-inducing capacity also enhanced omega oxidation of endogenous leukotriene B4, suggesting an additional inactivation of the chemotactic potential . Our data suggest that both hemolysins of P . aeruginosa contribute to the pathogenicity of P . aeruginosa by inducing and modulating inflammatory-mediator release from various cells.

J Biol Chem, 1989 Jun 5, 264(16), 9380 - 5
Purification and characterization of guanosine diphospho-D-mannose dehydrogenase . A key enzyme in the biosynthesis of alginate by Pseudomonas aeruginosa; Roychoudhury S et al.; Alginate-producing Pseudomonas aeruginosa are usually associated with the cystic fibrosis lung environment and contribute to the high mortality rates observed among these patients . The present paper describes the purification and enzymatic properties of guanosine diphospho-D-mannose dehydrogenase (EC 1.1.1.132), a key enzyme in alginate biosynthesis by mucoid P . aeruginosa . The enzyme was overproduced using a plasmid vector containing algD (the gene encoding this enzyme) under control of the tac promoter . It was purified from cell-free lysates by lowering the pH to 5.0, heating the extract to 57.5 degrees C for 10 min, and discarding the protein pellet . The enzyme was selectively precipitated from the supernatant fraction with 45% acetone, resuspended in a 100 mM triethanolamine acetate buffer, pH 7.6, and ultimately purified by Bio-Sil TSK-400 gel filtration chromatography . The subunit molecular weight (Mr 48,000) as well as the N-terminal amino acid sequence corresponded to those predicted from the DNA sequence of algD . The native protein migrated as a hexamer of 290,000 molecular weight upon Bio-Gel A-1.5m gel filtration chromatography . Kinetic analysis demonstrated an apparent Km of 14.9 microM for the substrate GDP-D-mannose and 185 microM for the cofactor NAD+ . GDP-D-mannuronic acid was identified as the enzyme reaction product . Several compounds (including GMP, ATP, GDP-D-glucose, and maltose) were found to inhibit enzymatic activity . GMP, the most potent of these inhibitors, exhibited competitive inhibition with an apparent Ki of 22.7 microM . Enzyme activity was also sensitive to the sulfhydryl group modifying agents iodoacetamide and p-hydroxymercuribenzoate . The addition of excess dithiothreitol restored enzyme activity, suggesting a possible involvement of cysteine residues in enzymatic activity.

Zh Mikrobiol Epidemiol Immunobiol, 1989 Jun, (6), 61 - 6
{Interferon in the modulation of the immune response in pyelonephritis caused by Staphylococci and Pseudomonas aeruginosa}; Pavlenko VA et al.; In experiments on mice the influence of mouse serum interferon, type I, on immune response in pyelonephritis caused by staphylococci and P . aeruginosa has been studied . The immunomodulating action of interferon and its therapeutic effectiveness have been shown to depend on the etiology of the disease . When injected intraperitoneally in a dose of 1,000 ED, interferon produces a pronounced therapeutic effect in pyelonephritis caused by P . aeruginosa and no effect in pyelonephritis of staphylococcal etiology . Type I interferon introduced in the dose used in this investigation has no influence on the killer activity of spleen lymphocytes, enhances the activity of the complement and the production of antibodies, produces a leukopenic effect and, depending on the etiology of pyelonephritis, exerts influence on the activity of dehydrogenases, the number of EAC- and E-rosette-forming cells, the oxidation metabolism of neutrophils and their phagocytic activity.

Mol Cell Probes, 1989 Jun, 3(2), 179 - 88
Development of gene probes and evolutionary relationships of the PSE-4 bla gene to plasmid-mediated beta-lactamases of gram-negative bacteria; Boissinot M et al.; Six types of plasmid-mediated carbenicillinases can be distinguished on the basis of their substrate profiles, molecular mass isoelectric values and immunological properties . As yet, no structural classification has been attempted for these enzymes at the molecular level . We have isolated the PSE-4 structural gene responsible for carbenicillinase production in Pseudomonas aeruginosa strain Dalgleish and studied its expression in E . coli . A detailed physical map of the cloned fragment and the construction of deletion mutants permitted the precise localization of the PSE-4 structural gene . Various restriction endonuclease fragments known to be flanking or internal to the PSE-4 bla gene were used as DNA probes and tested for homologous sequences in other beta-lactamase genes . A collection of three restriction fragment probes internal or delimiting the PSE-4 structural gene were hybridized with purified plasmid DNA coding for 18 other beta-lactamases . Under high stringency conditions, only the PSE-1, CARB-3 and CARB-4 genes cross-hybridized with PSE-4; while one of the probes tested hybridized solely with CARB-3 . Further analysis indicated that the PSE-1, PSE-4, CARB-3 and CARB-4 bla genes are related and could presumably have evolved from a common progenitor.

Pathol Biol (Paris), 1989 Jun, 37(6), 754 - 8
{Contribution of experimental models to the treatment of respiratory tract infections}; Chidiac C et al.; The need for more effective and potentially less toxic antimicrobial agents than aminoglycosides for treatment of gram negative bacilli pneumonia specially Pseudomonas aeruginosa, explains the interest for experimental models of pneumonia . These models allow to study the efficacy and safety of antibiotics alone or in combination . Aminoglycosides and new quinolones are more effective than beta-lactams for life threatening infection with high inoculum, the only exception to this finding has been for N-formimidoyl thienamycin, whereas for less severe infections aminoglycosides and beta-lactams are equivalent in efficacy . In contrast to high inocula pneumonia, combining beta-lactams with aminoglycosides give additive of synergic benefits for treating low inocula . Experimental models allow to compare continuous versus intermittent administration of antibiotics, different regimens of the same antibiotics (single daily dose of aminoglycosides versus conventional administration) and new antiinfectious agents as anti-pseudomonas hyperimmune globulins.

Arzneimittelforschung, 1989 Jun, 39(6), 694 - 7
Chemotherapeutic efficacy of ofloxacin against experimental pneumonia with Pseudomonas aeruginosa in guinea pigs; Otani T et al.; The chemotherapeutic efficacy of ofloxacin against experimental pneumonia was investigated with special reference to its treatment regimen . A pneumonia model was successfully produced by inhalation of a virulent strain of Pseudomonas aeruginosa in guinea pigs immunosuppressed with cortisone acetate . One or 4 days after infection, the animals were treated orally with the fixed daily doses of ofloxacin either once a day or thrice a day for 3 consecutive days . Ofloxacin given thrice a day eliminated the organisms from the lung more efficiently than the equivalent total doses injected once a day in both series of treatment, starting 1 or 4 days after infection . The superiority of the triple dosing in chemotherapeutic efficacy of ofloxacin was found to be attributable at least to the longer retention of its pulmonary levels exceeding the antibiotic concentrations.

DICP, 1989 Jun, 23(6), 456 - 60
Serum inhibitory and bactericidal activity of ciprofloxacin following intravenous administration; Dudley MN et al.; Serum inhibitory and bactericidal titers were measured in nine healthy volunteers following single iv doses of ciprofloxacin 100, 150, and 200 mg . The median peak serum bactericidal titer (5 minutes following completion of a 30-minute infusion) against two highly susceptible strains of Escherichia coli ranged between 1:64 and 1:1024 and titers exceeded 1:8 for six hours for all dose levels . The bactericidal titers against two strains of Pseudomonas aeruginosa and a methicillin-resistant strain of Staphylococcus aureus were considerably lower, the median peak being 1:2 at all dose levels . Measured inhibitory and bactericidal titers at five minutes and one hour postinfusion were significantly greater than those predicted (measured serum ciprofloxacin concentration to minimum inhibitory concentration {MIC} or minimum bactericidal concentration {MBC}) for only one strain of E . coli . Intravenous doses of ciprofloxacin 100-200 mg produce high and sustained serum bactericidal titers against highly susceptible bacteria; considerably lower levels of activity are seen against bacteria having higher MICs and MBCs but still considered susceptible to the drug.

J Dermatol Surg Oncol, 1989 Jun, 15(6), 633 - 7
Treatment of Pseudomonas aeruginosa auricular perichondritis with oral ciprofloxacin; Noel SB et al.; Pseudomonas aeruginosa auricular perichondritis can be a serious and expensive postoperative infection requiring prolonged hospitalization and intravenous administration of antibiotics . Oral antimicrobial agents have not been effective in the treatment of serious P . aeruginosa infections . Recently completed clinical trials have shown that oral ciprofloxacin, one of the new fluoroquinolone antimicrobials, is effective in the treatment of certain P . aeruginosa infections . We report two cases of P . aeruginosa auricular perichondritis successfully treated as outpatients with oral ciprofloxacin . This article also reviews the salient features of the new fluoroquinolones and their impact on antimicrobial therapy of serious skin and skin-structure infections.

J Bacteriol, 1989 Jun, 171(6), 3385 - 90
Recruitment of a chromosomally encoded maleylacetate reductase for degradation of 2,4-dichlorophenoxyacetic acid by plasmid pJP4; Kukor JJ et al.; When Pseudomonas aeruginosa PAO1c or P . putida PPO200 or PPO300 carry plasmid pJP4, which encodes enzymes for the degradation of 2,4-dichlorophenoxyacetic acid (TFD) to 2-chloromaleylacetate, cells do not grow on TFD and UV-absorbing material with spectral characteristics of chloromaleylacetate accumulates in the culture medium . Using plasmid pRO1727, we cloned from the chromosome of a nonfluorescent pseudomonad, Pseudomonas sp . strain PKO1, 6- and 0.5-kilobase BamHI DNA fragments which contain the gene for maleylacetate reductase . When carrying either of the recombinant plasmids, pRO1944 or pRO1945, together with pJP4, cells of P . aeruginosa or P . putida were able to utilize TFD as a sole carbon source for growth . A novel polypeptide with an estimated molecular weight of 18,000 was detected in cell extracts of P . aeruginosa carrying either plasmid pRO1944 or plasmid pRO1945 . Maleylacetate reductase activity was induced in cells of P . aeruginosa or P . putida carrying plasmid pRO1945, as well as in cells of Pseudomonas strain PKO1, when grown on L-tyrosine, suggesting that the tyrosine catabolic pathway might be the source from which maleylacetate reductase is recruited for the degradation of TFD in pJP4-bearing cells of Pseudomonas sp . strain PKO1.

Neth J Med, 1989 Jun, 34(5-6), 233 - 42
Cefsulodin for the treatment of Pseudomonas infections--a study comparing cefsulodin and ticarcillin; van der Meer JW et al.; The efficacy of cefsulodin against infections caused by Pseudomonas aeruginosa was investigated first in an open trial and then in a controlled comparative study in which ticarcillin was used . The first trial consisted of 16 patients with proven Pseudomonas aeruginosa infections, 9 of whom also received an aminoglycoside . In the second trial 28 such patients were evaluated (14 on cefsulodin 1 g 4 times daily and 14 on ticarcillin 5 g 4 times daily); all patients also received an aminoglycoside . The results of the two trials were similar in that 75% of the patients of the first trial and 86% of the second group exhibited an excellent or good response to cefsulodin . For the ticarcillin group a similar response was noted . In the first trial the sensitivity of P . aeruginosa did not change markedly, whereas one strain of the cefsulodin group became resistant in the second trial . Pharmacokinetic data were in agreement with those reported in the literature . Side effects were rare.

Unfallchirurg, 1989 Jun, 92(6), 305 - 8
{Rib span-plasty in sequestered osteomyelitis of the femoral diaphysis}; Pip M et al.; A case is reported of a 6-year-old boy with acute pyogenic osteomyelitis . A delay in making the diagnosis or inadequate early treatment led to chronic osteomyelitis . A delay in making a diagnosis is the most important factor in the prognosis of acute osteomyelitis . Sophisticated techniques are only indicated to detect and confirm the nature of the lesion, but they should not delay identification of the causative organisms . In our case, the diagnosis was delayed, and there was complete sequestration of the femur shaft as a result of insufficient early treatment . After diagnosis, the initial step was surgical debridement . After complete necrotomy, continuous irrigation with suction drainage was begun . To fill the defect and accelerate bone reconstruction, we performed an autogenous graft taking the 8th rib and splitting it into nine fragments . After identification of Pseudomonas aeruginosa as the causative organism, parenteral antibiotic therapy was begun and maintained . Nine weeks after admission, the boy was able to leave the hospital . Ten weeks later he was examined in the outpatient clinic and was walking and running quite normally . To date, there has been no recurrence of the infection.

Infect Immun, 1989 Jun, 57(6), 1792 - 9
Protective effect of recombinant murine granulocyte-macrophage colony-stimulating factor against Pseudomonas aeruginosa infection in leukocytopenic mice; Tanaka T et al.; The effects of recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) against Pseudomonas aeruginosa infection in ICR mice were investigated . Mice were treated with cyclophosphamide (CPA) and were then injected intraperitoneally with rmGM-CSF three times daily, beginning on the day after CPA treatment, for 7 days . The number of peripheral blood leukocytes in both CPA- and rmGM-CSF-treated mice and control CPA-treated mice reached a nadir on day 4, when P . aeruginosa was injected intraperitoneally . The administration of rmGM-CSF significantly increased the proportion of survivors among mice infected with a lethal dose of P . aeruginosa . This effect was further analyzed by monitoring sequential changes in leukocyte count and bacterial growth in various organs . The number of bacteria in the peritoneal cavities, peripheral blood samples, and livers of GM-CSF-treated mice decreased to an undetectable level after a transient increase, and the number was significantly lower than that in control mice . In GM-CSF-treated mice, the neutrophil levels in peripheral blood started to increase 5 days after CPA administration and were consistently higher than those in controls . Furthermore, the neutrophils in GM-CSF-treated mice were more mature morphologically . Thus, the prophylactic effect of rmGM-CSF against P . aeruginosa infection may result from a rapid recovery of myelopoiesis and a partial enhancement of mature neutrophil function.

Zh Mikrobiol Epidemiol Immunobiol, 1989 Jun, (6), 3 - 8
{Protective properties of anatoxin obtained from a homogeneous preparation of Pseudomonas aeruginosa exotoxin A}; Brodinova NS et al.; The protective properties of formulated toxoid obtained from the highly purified preparation of P . aeruginosa exotoxin A have been studied in the test of the active immunization of mice . The study has revealed that the preparation when introduced in 1 or 2 injections in a dose of 15 micrograms, shows faint protective potency with respect to P . aeruginosa strains differing in virulence . Immunization with this toxoid in 3 and 4 injections has been found to ensure 60-100% and 50-60% protection of mice infected with P . aeruginosa toxigenic and proteolytic strains respectively . Immunization with toxoid has been found to induce the appearance of short-term antibacterial immunity which loses its capacity to protect the immunized animals, challenged with both toxigenic and proteolytic P . aeruginosa strains, as early as on day 28 . The immunization of mice with toxoid in 4 injections has been shown to induce the development of antitoxic immunity capable of neutralizing up to 150 LD50 of purified exotoxin A.

Korean J Ophthalmol, 1989 Jun, 3(1), 11 - 3
Antibacterial effect of tetracaine hydrochloride (Pontocaine) in the aspect of exposure time--in vitro study; Kang SW et al.; Antibacterial effect of tetracaine hydrochloride was studied . Tetracaine hydrochloride (preservative free) were incubated with Staphylococcus aureus, coagulase negative staphylococcus and Pseudomonas aeruginosa respectively, for 18 hours and for 2 minutes . Then it was diluted and cultured on nutrient agar plate . Colony counts were done after 18 hours . In case of 18 hours incubation, there was no growth of microbials in 0.5%, 0.1% tetracaine hydrochloride, but there was no inhibitory effect of 0.02% tetracaine hydrochloride on growth of microbials, irrespective of inoculum amount . In case of 2 minutes incubation with 0.5% tetracaine hydrochloride, there was no difference between the amount of microbial inoculum and colony count . Above indicates that tetracaine hydrochloride has no inhibitory effect on bacterial growth after short exposure of less than 2 minutes.

Immunol Cell Biol, 1989 Jun, 67 ( Pt 3), 169 - 76
Eicosanoids produced during interactions between Pseudomonas aeruginosa and alveolar macrophages are species-dependent; Sorrell TC et al.; Eicosanoid production during phagocytosis of pyogenic bacteria by rabbit alveolar macrophages was studied as a model of early events in the pathogenesis of pneumonia . Adherent alveolar macrophages, prelabelled with {3H}-arachidonic acid (AA), were incubated with live, opsonized Staphylococcus aureus or Pseudomonas aeruginosa (bacteria:macrophage ratio of 50:1) at 37 degrees C for 90 min . Supernatant eicosanoids were extracted and separated by reverse phase high performance liquid chromatography (RP-HPLC) . While the amounts of labelled PGE2, TXB2, and PGD2 produced in response to the two organisms were equal, the amount of PGF2 alpha elicited by S . aureus amounted to three times that released during macrophage challenge with P . aeruginosa . Overall, preferential release of cyclooxygenase products occurred during phagocytosis of S . aureus . In contrast, eicosanoids identified presumptively as oxygenated metabolites of AA predominated in cultures challenged with opsonized P . aeruginosa . Live, non-opsonized P . aeruginosa elicited the same profile of eicosanoids, but in reduced amounts . Inhibitor studies indicated that these AA derivatives were not synthesized via the macrophage lipoxygenase pathway . Their production was dependent on the viability of P . aeruginosa . Macrophages challenged with opsonized, heat-killed P . aeruginosa resulted in production of an eicosanoid profile similar to that elicited by S . aureus . Secondary metabolism by P . aeruginosa of eicosanoids released from the macrophage did not contribute to the unique profile produced during the interaction of this organism with labelled macrophages . Our data indicate that during binding to macrophages, the primary human pathogen, P . aeruginosa, specifically modulates the profile of eicosanoids produced . This effect on inflammatory mediators may be of biological significance in the pathogenesis of pneumonia.

Can J Microbiol, 1989 Jun, 35(6), 630 - 5
Isolation and characterization of a Pseudomonas aeruginosa bacteriophage with a very limited host range; Bigby D et al.; A Pseudomonas aeruginosa bacteriophage, phi PLS743, with extremely limited host range has been isolated . It belongs to the virus family Podoviridae, morphological type C1, and possesses a head diameter of 45 nm . The phage has a buoyant density in CsCl of 1.516 g/cm3, and its mass is 45 x 10(6) daltons . The phage particles are composed of double-stranded DNA (49.9 mol% G + C; 42.4 kilobase pairs) and 11 structural proteins (66% by weight) . The major head protein, P5, has a Mr of 34,500 . The DNA is not cut by SalI or XhoI restriction endonucleases, but is cut by PvuII (1 site), KpnI and BglII (2 sites), PvuI (4 sites), BamHI (7 sites), EcoRI (9 sites), and HindIII (12 sites) . A restriction endonuclease map is presented.

Anasth Intensivther Notfallmed, 1989 Jun, 24(3), 167 - 71
{Adjuvant therapy with pseudomonas immunoglobulin in artificially ventilated patients at a surgical intensive care unit}; Class I et al.; Preoperative hospitalism and postoperative respiratory therapy together with antibiotical prophylaxis are risk factors for pulmonary infection due to Pseudomonas aeruginosa . Psomaglobin, a new Pseudomonas hyperimmune globulin, was given to 25 postoperative or posttraumatic patients during a prospective randomized study as an additional therapy for severe Pseudomonas infection . Respiratory therapy and therefore residence in the ICU were markedly shorter in the therapy (n = 25) than in the control group (n = 20).

Zentralbl Veterinarmed B, 1989 Jun, 36(4), 292 - 6
{O-serovar distribution and antibiotic sensitivity of Pseudomonas aeruginosa strains from birds and reptiles}; Schildger BJ et al.; 100 strains of Pseudomonas aeruginosa (P.a.) from birds and reptiles were compared by determination of their O-serovars and their resistance to chemotherapeutic agents . A great number of isolates (birds 17.4%, reptiles 29.6%) were serologically untypable using 17 O-antisera by slide-agglutination-technique . The prevalence of O-serovar 0:6 was found in birds (39%) and reptiles (18.5%), followed by bird-isolates 0:1 and 0:3 (each 13%) and reptile-isolates 0:16 (14.8%) . The serological distribution was different among bird- and reptile-isolates and also among the human and animal strains . All strains were resistant to penicillin G and ampicillin, more than 90% to nitrofurantoin, sulfamethoxazole-trimethoprim, chloramphenicol and erythromycin . Resistance to tetracycline was found to be 87%, resistance to sulfonamide 81%, respectively . 32% of all isolates were resistant to streptomycin, 61% to kanamycin . All isolates were susceptible to genta- and neomycin . Also all isolates, except one reptile-strain, were susceptible to gyrase-blocker (Bay VP 2674) . 2 isolates were resistant to polymyxin B.

J Clin Microbiol, 1989 Jun, 27(6), 1367 - 71
Amount, avidity, and specificity of antibodies to Pseudomonas aeruginosa in normal human sera; Grzybowski J et al.; Seventy-two normal human sera from healthy blood donors were tested by an enzyme-linked immunosorbent assay in order to determine the amounts and avidities of immunoglobulins M and G antibodies to lipopolysaccharides of seven Fisher's immunotypes of Pseudomonas aeruginosa and to exotoxin A . The patterns of specificity for seven immunotypes in all individual sera were determined . These data show a predominance of antibodies directed to Fisher's immunotypes 7 and 4 in the human population tested and may reflect frequency of occurrence of immunotypes outside the hospital environment.

J Clin Microbiol, 1989 Jun, 27(6), 1222 - 9
Antilipopolysaccharide antibodies and differential diagnosis of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis; Fomsgaard A et al.; Chronic lung infection in cystic fibrosis is characteristically associated with polyagglutinable, serum-sensitive, mucoid strains of Pseudomonas aeruginosa . Enzyme-linked immunosorbent assay (ELISA) methods for standard-free quantitation of immunoglobulin G (IgG) and IgM antibodies to P . aeruginosa lipopolysaccharides (LPSs) have been developed . We now report the development of assays for quantitation of monomer and dimer total IgA and IgA anti-LPS antibodies . Use of these methods in diagnosis of early chronic P . aeruginosa lung infection was assessed . IgG and IgA anti-LPS levels increased significantly at the onset of chronic infection and continued to increase to very high levels in the later stages of infection . IgM anti-LPS levels also rose at the onset of chronic infection but did not increase further . The function of true- and false-positive rates was illustrated by using various concentrations of IgG, IgA, and IgM anti-LPS for discrimination of patients . Values that gave optimum separations were used for statistical evaluation of the diagnostic sensitivities and specificities of anti-LPS antibody concentrations . The results obtained in these assays were compared with a diagnosis, based on the number of precipitins in crossed immunoelectrophoresis, of serum samples from cystic fibrosis patients . In 64 paired serum samples taken before and immediately after the onset of chronic infection, as defined by crossed immunoelectrophoresis precipitins, the predictive values of a positive ELISA were 86% for IgG and 89% for IgA . The predictive values for a negative ELISA were 98% for IgG and 97% for IgA . Results of the IgM anti-LPS ELISA had a lower predictive value . Immunoblotting and absorption studies showed that IgG anti-LPS antibodies were directed specifically against LPS of P . aeuruginosa . ELISAs were developed to determine the specific IgG sublclasses involved . The increase in IgG anti-LPS involved all four subclasses . Highest anti-LPS titers were seen with IgG1 and IgG4, but the largest relative increases were seen with IgG2 and IgG3.

Invest Ophthalmol Vis Sci, 1989 Jun, 30(6), 1069 - 74
A partial-thickness epithelial defect increases the adherence of Pseudomonas aeruginosa to the cornea; Klotz SA et al.; Some patients with infectious keratitis have no clinically demonstrable corneal abrasion predisposing them to infection . Subtle, undetectable corneal injuries may facilitate bacterial adherence to the cornea, eventually leading to keratitis . To study this concept, we have developed a rabbit model in which a partial-thickness corneal epithelial defect was induced by filter paper impression on the cornea that removed one to two layers of corneal epithelium . Following this injury, the corneas were incubated with Pseudomonas aeruginosa, washed, and the number of bacteria adhering to the injured corneas as well as to control corneas was quantitated . Corneas treated with filter paper, either ex vivo or in vivo, allowed 20 times more bacteria to adhere than did the untreated control corneas (P less than 0.01) . This superficial epithelial defect increased Pseudomonas adherence to the cornea for up to 72 hr after injury . When corneal injury was extended to the stroma, the adherence of Pseudomonas was further augmented as compared to adherence to the superficially injured cornea . Thus, we conclude that a clinically subtle, partial-thickness corneal epithelial injury can markedly facilitate the adherence of Pseudomonas aeruginosa, which may be an important predisposing factor for infectious keratitis.

J Bacteriol, 1989 Jun, 171(6), 3304 - 9
Pseudomonas aeruginosa outer membrane protein F: structural role and relationship to the Escherichia coli OmpA protein; Woodruff WA et al.; A Pseudomonas aeruginosa outer membrane protein F-deficient omega-insertion mutant strain H636, in contrast to its protein F-sufficient parent strain H103, was unable to grow on unsupplemented Proteose Peptone no . 2 broth (Difco Laboratories, Detroit, Mich.) . Addition of high concentrations of NaCl, KCl, glucose, sucrose, or potassium succinate permitted growth of strain H636 at rates approaching those of the parent strain H103 . Strain H636 cells were 33% shorter and had a 46% smaller cross-sectional area than did the parent strain growing at similar rates on the same medium . These properties of the oprF::omega mutant were analogous to those previously observed for Escherichia coli ompA mutants in an lpp (Braun lipoprotein-deficient) mutant background . Therefore, we compared P . aeruginosa protein F and the E . coli OmpA protein . In addition to many similarities previously described, sequence alignment demonstrated substantial amino acid sequence homology throughout the carboxy-terminal 168 to 180 amino acids of the two proteins . Consistent with this observation, polyclonal antiserum specific for OmpA reacted on Western blots (immunoblots) with protein F . Expression of protein F from the cloned oprF gene in an E . coli ompA lpp double mutant resulted in a 1.7-fold increase in cell length and a 2.1-fold increase in cross-sectional area compared with values for the same mutant containing only the plasmid vector onto which the oprF gene had been cloned . These results favor a structural role for P . aeruginosa protein F and suggest that it is strongly related to the E . coli OmpA protein.

J Bacteriol, 1989 Jun, 171(6), 3211 - 7
Outer membrane protein H1 of Pseudomonas aeruginosa: purification of the protein and cloning and nucleotide sequence of the gene; Bell A et al.; Overexpression of the divalent cation-regulated outer membrane protein H1 of Pseudomonas aeruginosa is associated with resistance to polymyxin B, aminoglycosides, and EDTA . Protein H1 is believed to act by replacing divalent cations at binding sites on lipopolysaccharide, thereby preventing disruption of the sites and subsequent self-promoted uptake of the antibiotics . Protein H1 purified by two cycles of anion-exchange chromatography was apparently associated with lipopolysaccharide . Lipopolysaccharide-free protein H1 was purified in high yield by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was subjected to N-terminal amino sequencing . Complementary oligodeoxyribonucleotides were used to clone the structural gene for protein H1, oprH, into Escherichia coli . Successful cloning was confirmed by nucleotide sequence analysis . Southern hybridization suggested that oprH was present as a single-copy gene in P . aeruginosa . The deduced amino acid sequence revealed that H1 was a slightly basic polypeptide of 178 residues, with a leader sequence typical of an exported procaryotic protein . It had little similarity, however, to other bacterial surface proteins for which sequence data were available . No expression of protein H1, from its own or the lac promoter, was detected in E . coli . We concluded that, as for some other regulated Pseudomonas genes, expression of oprH, at least under some conditions, is blocked in E . coli.

Infect Immun, 1989 Jun, 57(6), 1707 - 13
Complement activation and C3 binding by serum-sensitive and serum-resistant strains of Pseudomonas aeruginosa; Schiller NL et al.; The relationship among complement consumption, C3 deposition, and C3 fragmentation pattern was compared for serum-sensitive (Sers) and serum-resistant (Serr) strains of Pseudomonas aeruginosa . The Sers strains, which were mucoid strains derived from patients with cystic fibrosis, had lipopolysaccharide deficient in O-antigen side chains . These organisms generally activated much less complement per organism than their Serr counterparts, characterized by the presence of lipopolysaccharide with long lipopolysaccharide O side chains . Surprisingly, however, although the Serr strains consumed more total hemolytic complement, less C3 was deposited onto the surface of these strains than onto that of the Sers strains . Maximal C3 binding required the participation of both the classical and alternative complement pathways, although classical complement pathway involvement was more important for Serr strains . Finally, while more than half of the C3 deposited on most Sers strains was in the form of C3b, most of the C3 on the Serr strains was in the form of iC3b, indicating a more rapid and extensive conversion of C3b to iC3b on the surface of these strains . Limited complement activation by Sers mucoid strains of P . aeruginosa may confer a selective survival advantage to these organisms in colonizing the airways of patients with cystic fibrosis.

Infect Immun, 1989 Jun, 57(6), 1691 - 6
Heterogeneity of the L-rhamnose residue in the outer core of Pseudomonas aeruginosa lipopolysaccharide, characterized by using human monoclonal antibodies; Yokota S et al.; Hybridoma cell lines producing human monoclonal antibodies (MAbs) MH-4H7 and KN-2B11 {immunoglobulin M (lambda)} which bound to the outer core region of Pseudomonas aeruginosa lipopolysaccharide (LPS) were established by cell fusion of human peripheral lymphocytes with human-mouse heteromyeloma SHM D-33 . Both binding specificity experiments with a series of LPS-defective mutants derived from P . aeruginosa PAC1R (P . S . N . Rowe and P . M . Meadow, Eur . J . Biochem.132:329-337, 1983) and competitive enzyme immunoassay experiments with monosaccharides demonstrated that alpha-L-rhamnose residues in the outer core of LPS might be in part an epitope . The MAbs specifically bound to clinical isolates belonging to Homma serotypes A, F, G, and K at a frequency of 70 to 86% and to serotypes H and M isolates at about 50% . They did not bind to any isolates of serotype B, E, and I tested . This evidence indicates that L-rhamnose and probably its neighboring residues in the other core of P . aeruginosa are heterogeneous in some association with the O serotype.

Infect Immun, 1989 Jun, 57(6), 1668 - 74
Inactivation of human gamma interferon by Pseudomonas aeruginosa proteases: elastase augments the effects of alkaline protease despite the presence of alpha 2-macroglobulin; Horvat RT et al.; Pseudomonas aeruginosa alkaline protease (AP) has recently been shown to produce limited proteolysis of human gamma interferon (IFN-gamma) and thereby destroy the antiviral and macrophage-activating activities of the lymphokine . In the present study we describe some of the characteristics of Pseudomonas elastase (E) with regard to inactivation of human IFN-gamma . The inhibitory effect of E on IFN-gamma bioactivity differed from that of AP in that the direct effects of E were reduced in the presence of human serum . That this property of human serum was in large part attributable to the protease inhibitor alpha 2-macroglobulin (alpha 2-M) was suggested by the following observations: (i) methylamine treatment of serum reduced its effect on E, (ii) E interacted directly with alpha 2-M to induce a characteristic conformational change in the protease inhibitor, and (iii) preformed E-alpha 2-M complexes lacked IFN-gamma-degrading activity . Despite these findings, anti-E antiserum partially neutralized the effect that a Pseudomonas filtrate showed on IFN-gamma, suggesting that E contributes to the activity of bacterial filtrates . Treatment of IFN-gamma with E in the presence of a suboptimal concentration of AP resulted in an E dose-dependent inactivation of the lymphokine . Preformed E-alpha 2-M complexes, although ineffective by themselves at cleaving IFN-gamma, degraded the lymphokine, providing AP was also present in the reaction mixture . These data demonstrate that the destruction of small, biologically significant peptides by Pseudomonas proteases can involve protease-protease synergy that acts even in the presence of the serum protease inhibitor alpha 2-M.

J Biol Chem, 1989 May 25, 264(15), 9004 - 8
Several GTP-binding proteins, including p21c-H-ras, are preferred substrates of Pseudomonas aeruginosa exoenzyme S; Coburn J et al.; Pseudomonas aeruginosa exoenzyme S has appeared to be relatively indiscriminate in its choice of substrates, but in fact it ADP-ribosylates only a small subset of cellular proteins and exhibits a marked preference for several different membrane-associated proteins of apparent Mr = 23,000-25,000, at least some of which appear to bind GTP . One of these is the p21 product of the proto-oncogene c-H-ras, which can be labeled to completion . ADP-ribosylation does not alter the interaction of p21c-H-ras with guanyl nucleotides, but does cause a shift in electrophoretic mobility that implies a large conformational change . Exoenzyme S modifies all of its substrates at arginine residues.

Gene, 1989 May 15, 78(1), 1 - 8
Nucleotide sequence and expression of a cloned Thiobacillus ferrooxidans recA gene in Escherichia coli; Ramesar RS et al.; The nucleotide sequence of the recA gene of Thiobacillus ferrooxidans has been determined . No SOS box characteristic of LexA-regulated promoters could be identified in the 196-bp region upstream from the coding region . The cloned T . ferrooxidans recA gene was expressed in Escherichia coli from both the lambda pR and lac promoters . It was not expressed from the 2.2-kb of T . ferrooxidans DNA preceding the gene . The T . ferrooxidans recA gene specifies a protein of 346 amino acids that has 66% and 69% homology to the RecA proteins of E . coli and Pseudomonas aeruginosa, respectively . Most amino acids that have been identified as being of functional importance in the E . coli RecA protein are conserved in the T . ferrooxidans RecA protein . Although some amino acids that have been associated with proteolytic activity have been substituted, the cloned protein has retained protease activity towards the lambda and E . coli LexA repressors.

Zhonghua Wai Ke Za Zhi, 1989 May, 27(5), 292 - 3, 317
{Analysis of 240 cases of burn patients with Pseudomonas aeruginosa septicemia}; Yang XD; This paper analyses 240 cases of burn patients with pseudomonas (Ps) aeruginosa septicemia . They were admitted to our hospital from 1959 to 1988 . The morbidity, time of episode of septicemia, mortality and relationship between the mortality and burned surface area are surveyed . The author considers that Ps . aeruginosa septicemia is a significant factor which burned patient dies of.

Acta Paediatr Scand, 1989 May, 78(3), 395 - 404
Estimated risk of cross-infection with Pseudomonas aeruginosa in Danish cystic fibrosis patients; Hoiby N et al.; During the period 1970-1987 the number of cystic fibrosis (CF) patients treated at the Danish CF Center increased from 54 to 226 . The prevalence of patients with chronic P . aeruginosa infection (CF + P) increased from 35% to 59%, whereafter it decreased to 54% . The yearly incidence of new CF + P patients averaged 8.4% in 1970-1975, 17% in 1976-80, 6.5% in 1981-85, and 3% in 1986-87 . These changes correlated to the increased "contact density" between CF + P and non-infected CF patients (CF-P) due to intensified treatment starting in 1976, and the reduced "contact density" due to separation of the two groups starting in 1981 . The same trends were observed during an epidemic spread of a multiply resistant P . aeruginosa in the CF + P group, which was also interrupted by separation of two groups of patients, with and without the multiply resistant strain . The observed prevalences of CF + P in different age groups of patients are in accordance with a 20% incidence/year in patients older than three years . The highest probability of acquiring chronic P . aeruginosa infection was calculated to be 2%/day and the lowest 0.09%/day spent in the Centre . By employing a simple mathematical model of the spread of infectious diseases it can be shown, that the highest incidence of CF + P is present when the prevalence of CF + P is 20-80%, and that an increase in the total number of patients also increases the incidence of CF + P unless the patients are divided into smaller groups . The observations in the Danish CF Centre are in accordance with this model.

Pathol Biol (Paris), 1989 May, 37(5), 500 - 3
{Treatment of superinfections caused by pyocyanic bacillus in patients with mucoviscidosis . Efficacy of cefsulodin in combination with an aminoglycoside}; Jehanne M; Cefsulodin is a third generation cephalosporin with specific antipseudomonas activity . We used cefsulodin in combination with aminoglycosides in 15 cystic fibrosis patients treatments . There were 13 children or adolescents, 4 to 19 years old with chronic Pseudomonas aeruginosa lung infections: 9 patients had acute exacerbations of infection with occasionally important respiratory insufficiency and 5 patients had a regimen of regular treatment every 3 months . Cefsulodin was given after record of bacterial sensitivity to antibiotics, at the mean posology of 100 mg/kg, IV, tid . The combination with aminoglycosides was systematic: tobramycin (6 mg/kg/day), netilmicin (6 mg/kg/day) or amikacin (30 mg/kg/day) . Duration of treatment was 9 to 15 days . Results:--clinical improvement in all patients, important in 13 patients and moderate in 2 patients;--respiratory function improvement in 11 patients;--pulmonary radiography improvement in 10 patients;--Pseudomonas were eradicated in 8 patients but temporarily and were found after treatment in 7 patients, 5 with lower number, 2 with higher number . Clinical and biological tolerance was excellent . The present study shows the interest of cefsulodin use in combination with aminoglycosides in this pathology.

Orthop Rev, 1989 May, 18(5), 581 - 5
Bacterial osteomyelitis . Adjunctive hyperbaric oxygen therapy; Mader JT et al.; Mechanistically, hyperbaric oxygen (HBO) appears useful for the treatment of osteomyelitis . HBO increases the oxygen tension in infected tissue, including bone . An adequate oxygen tension is necessary for oxygen-dependent killing of organisms by polymorphonuclear leukocytes, and for fibroblast activity leading to angiogenesis and wound healing . In addition, HBO augments the killing of Pseudomonas aeruginosa by the aminoglycoside tobramycin . At the University of Texas Medical Branch in Galveston, adjunctive HBO is used for Cierny-Mader stage 3B and 4B osteomyelitis.

J Pediatr, 1989 May, 114(5), 767 - 73
Clinical and genetic comparisons of patients with cystic fibrosis, with or without meconium ileus; Kerem E et al.; We set out to determine if the clinical course or genetic profiles of patients with cystic fibrosis who had meconium ileus differed from those of other patients with cystic fibrosis . Since 1950 we have followed 158 patients with meconium ileus among 1175 patients with cystic fibrosis (13.4%) . Patients with meconium ileus had lower birth weight (3026 +/- 610 gm) than patients with no meconium ileus (3169 +/- 534 gm; p less than 0.008); the deficit was especially evident in female patients . Survival in the first year of life increased from 55% in those born between 1958 and 1972 to 96% in those born between 1973 and 1987 . Since 1973 the median survival of male and female patients with meconium ileus was similar to that in female patients with no meconium ileus (21 years), whereas 78% of males with no meconium ileus survived to this age (p less than 0.0001) . Patients with meconium ileus born before 1972 had lower weight and height percentiles at age 13 years compared with patients with no meconium ileus, but this difference was not as apparent in patients born after 1973 . There were no differences between the two groups in forced vital capacity, forced expiratory volume in 1 second, or forced expiratory flow in the middle half of forced vital capacity . Patients with meconium ileus acquired Pseudomonas aeruginosa at a younger age than did patients with no meconium ileus (4.20 +/- 4.67 vs 7.18 +/- 5.19 years), but there was no difference in age of acquisition of P . cepacia . In families in which the first child had meconium ileus, 29% of subsequent siblings with cystic fibrosis had meconium ileus, compared with 6% of siblings born to families in which the first child did not have meconium ileus . Allelic frequencies and haplotypic variants for cystic fibrosis chromosomes with respect to DNA markers closely linked to the cystic fibrosis locus were similar in families with cystic fibrosis with meconium ileus and those with no meconium ileus . These findings suggest that patients with cystic fibrosis and those without meconium ileus do not have major intrinsic differences and that the previously poor outlook in patients with meconium ileus has improved greatly.

Antonie Van Leeuwenhoek, 1989 May, 56(1), 35 - 45
Quinoprotein ethanol dehydrogenase from Pseudomonas; Gorisch H et al.; Dye-linked ethanol dehydrogenases from Pseudomonas aeruginosa ATCC 17,933 and P . putida ATCC 17,421 were purified to homogeneity and crystallized . The amino acid composition of the two enzymes is very similar and the number of the aromatic amino acid residues found per subunit are almost identical . With respect to their catalytic and molecular properties both ethanol dehydrogenases are similar to the quinoprotein methanol dehydrogenases known from methylotrophic bacteria . They show a high pH-optimum, need ammonia or an amine as activator and are dimers of identical subunits of a molecular mass of 60,000 . The dimer is the catalytically active form . Each subunit carries one prosthetic group pyrroloquinoline quinone, which can be titrated by the suicide substrate cyclopropanone ethylhemiketal . In contrast to the general methanol dehydrogenases the two ethanol dehydrogenases have a low affinity for methanol and in addition to primary alcohols they also oxidize secondary alcohols . With secondary alcohols preferentially one of the two enantiomers is oxidized . The catalytic and spectral properties of the two enzymes are very similar to the quinoprotein ethanol dehydrogenase isolated from P . aeruginosa LMD 80.53 (Groen et al., 1984 . Biochem . J . 223: 921-924) . However this enzyme is reported to be a monomer of molecular mass 100,000.

Laryngoscope, 1989 May, 99(5), 510 - 3
Ciprofloxacin for the treatment of chronic ear disease; Piccirillo JF et al.; The treatment of chronic ear disease is often difficult and frustrating . Patients typically present with a history of chronic, persistent otorrhea that has failed to respond to multiple topical and oral antibiotics . Organisms that are resistant to multiple antibiotics are common . Ciprofloxacin has been shown to be effective against a wide range of gram-negative and gram-positive organisms . To evaluate the role of ciprofloxacin in the treatment of chronic ear disease, 21 patients who failed routine therapy for chronic ear disease were prospectively treated with oral ciprofloxacin . Prior to therapy, all ear cultures grew Pseudomonas aeruginosa, Staphylococcus aureus or other gram-negative organisms . Ninety-five percent of patients completing therapy showed either improvement or cure . Only one patient failed to improve . Ciprofloxacin has been shown to be effective in the management of chronic ear disease.

J Infect Dis, 1989 May, 159(5), 945 - 53
Polyaspartic acid prevents experimental aminoglycoside nephrotoxicity; Gilbert DN et al.; The influence of the polyamino acid polyaspartic acid (PAA) on experimental aminoglycoside nephrotoxicity was determined . PAA prevented all measured functional and pathologic evidence of gentamicin nephrotoxicity for less than or equal to 27 d of study . All the animals given PAA, either alone or with gentamicin, developed prominent cytoplasmic vacuoles in the cells of the renal proximal convoluted tubules; the vacuoles in rats given just PAA differed from those observed in rats given PAA plus gentamicin . Rats given PAA plus gentamicin accumulated roughly 10 times more renal aminoglycoside as did rats given gentamicin alone . Immunohistochemical localization studies confirmed the presence of increased amounts of gentamicin in the cytoplasm of the tubular cells of animals given gentamicin plus PAA . PAA did not alter the in vitro antimicrobial activity of gentamicin versus Escherichia coli or Pseudomonas aeruginosa . These studies demonstrate the ability of PAA to prevent experimental gentamicin nephrotoxicity.

Indian Pediatr, 1989 May, 26(5), 466 - 71
Susceptibility of clinical isolates to cephalexin, cefazolin and cefotaxime; Gupta BL et al.; Three hundred and seventeen recent clinical isolates were tested for in vitro susceptibility to the three cephalosporins available in India--cephalexin, cefazolin and cefotaxime by the Kirby--Bauer disc diffusion method . Cefazolin was the most effective cephalosporin against Gram positive cocci (71.8% sensitive) followed by cefotaxime (62.7%) and cephalexin (52.7%) . Cefotaxime was very effective against commonly isolated Gram negative bacilli with only 10 (8.8%) isolates being resistant to it while 44 (39%) and 65 (57.5%) were resistant to cefazolin and cephalexin, respectively . All isolates of Pseudomonas aeruginosa were resistant to cephalexin and cefazolin and only 29 (32.6%) were sensitive to cefotaxime.

West J Med, 1989 May, 150(5), 545 - 7
Wound site as a predictor of complications following deep nail punctures to the foot; Patzakis MJ et al.; The site of injury, condition of the nail, and type of foot covering were compared in 36 inpatients and 34 outpatients with nail puncture wounds to the foot . Of the 36 inpatients, 34 (94%) had pyarthrosis, osteomyelitis, or both . The plantar surface of the foot was divided into 3 zones . Of the 36 inpatients, 35 (97%) had deep puncture wounds in zone 1 . In contrast, only 6 of 34 (18%) outpatients had injury to this area . Tennis shoes were shown to predispose to infection with Pseudomonas aeruginosa . Based on our findings, an early hospital admission should be considered for all patients with deep puncture wounds located in zone 1 and for patients who give a history of bone penetration in zone 2 or 3 at the time of injury . All patients who meet the above criteria and who are not admitted to hospital should be observed closely.

Vrach Delo, 1989 May, (5), 123 - 4
{Immune response of donors, previously hyperimmunized with staphylococcus anatoxin to Pseudomonas aeruginosa antigen}; Fedorovskaia EA et al.; The authors studied the immune response of the body of 23 donors formerly hyperimmunized with staphylococcal anatoxin to pyocyaneus antigen . It was established that immunization of these donors with Bacillus pyocyaneus anatoxin did not produce pathological reactions of the body, resulted in activation of the immune systems and production and antipyocyaneus antibodies.

Arch Fr Pediatr, 1989 May, 46(5), 331 - 4
{Iron deficiency and Pseudomonas aeruginosa colonization in cystic fibrosis}; de Montalembert M et al.; The incidence of iron deficiency and its relationship with the concentration or iron in sputum and the number of Pseudomonas aeruginosa (PA) colonies was studied in an unselected group of 53 cystic fibrosis (CF) patients with an age range of 3 months to 21 years . Parameters used to assess the iron status included serum iron, the % saturation of transferrin (n = 53) . The number of subjects with depletion of iron stores was estimated by levels of ferritin (n = 50) . The concentration of iron and of PA was measured in a subgroup (n = 24) and compared to a control group (n = 8) with pulmonary infections of varying etiology . A close correlation was found between serum iron and the % saturation of transferrin (r = 0.952; p less than 0.001) . Between 22.6 to 28.3% of patients were found to be iron deficient . An abnormally low ferritin (less than 12 ng/ml) was noted in 28% of cases but no correlation could be established between changes of serum iron and ferritin levels as a function of the degree of infection and/or of inflammation . In 62% of cases (n = 15) the concentration of iron in sputum was found to be within the range of control values (12-27 mumols/l) . In 38% of cases (n = 9), ferritin values were above 27 mumols/l . No correlation was found between the concentration of iron and the number of PA colonies in sputum . We can therefore conclude the following: 1) iron deficiency is more common in CF than previously reported; 2) ferritin levels constitute a poor index of iron deficiency; 3) colonisation with PA is not associated with iron content of bronchial secretions.

Anticancer Res, 1989 May-Jun, 9(3), 611 - 4
The bactericidal effect on Pseudomonas strains of adriamycin associated with quinolones; Castelli M et al.; The in vitro antibacterial activity of quinolone compounds was assessed on strains of Pseudomonas aeruginosa isolated from clinical infections . The bactericidal effect of quinolones was high and their respective antibacterial properties with adriamycin remained unimpaired on strains both sensitive and resistant to betalactam and aminoglycoside antibiotics . The cytotoxic effect of the combination of adriamycin and quinolones was determined in cultured P388 leukemia cells: no interference with the cytotoxic activity of adriamycin was observed.

Antimicrob Agents Chemother, 1989 May, 33(5), 624 - 34
Characterization of mechanisms of quinolone resistance in Pseudomonas aeruginosa strains isolated in vitro and in vivo during experimental endocarditis; Chamberland S et al.; Mechanisms of resistance to quinolones were characterized in Pseudomonas aeruginosa strains isolated after Tn5 insertional mutagenesis and in resistant strains that emerged during pefloxacin therapy of experimental aortic endocarditis . Quinolone resistance achieved in in vitro-selected mutants Qr-1 and Qr-2 was associated with cross-resistance to several groups of antimicrobial agents, including beta-lactams, tetracycline, and chloramphenicol . A significant reduction of norfloxacin uptake was also observed . After ether permeabilization of the cells, DNA synthesis of these two isolates was as susceptible to norfloxacin as DNA synthesis of the parent strain (PAO1) . These results indicate that alteration of outer membrane permeability is the primary determinant of resistance in these isolates . This altered cell permeability was correlated with reduction of outer membrane protein G (25.5 kilodaltons) and loss of a 40-kilodalton outer membrane protein in strain Qr-1 . Resistance to quinolones that emerged during experimental endocarditis therapy was associated with both modification of outer membrane permeability (decreased uptake of norfloxacin) and decreased susceptibility of DNA synthesis to norfloxacin . Resistance was limited to quinolones and chloramphenicol . For these strains, norfloxacin inhibitory doses (50%) for DNA synthesis were identical to the drug MICs, suggesting that despite the identification of a permeability change, perhaps due to changes of lipopolysaccharide, the alteration of the quinolone intracellular target(s) susceptibility constitutes the primary determinant of resistance . Also, two distinct levels of norfloxacin resistance of DNA synthesis were found in these isolates, indicating that at least two distinct alterations of the drug target(s) are possible in P . aeruginosa.

J Clin Microbiol, 1989 May, 27(5), 962 - 7
Occurrence of a common lipopolysaccharide antigen in standard and clinical strains of Pseudomonas aeruginosa; Lam MY et al.; The lipopolysaccharide (LPS) of Pseudomonas aeruginosa PAO1 contains two species of O polysaccharide termed A and B bands . The high-molecular-weight B-band LPS determines the O specificity of the bacterium, while the antigenically distinct A-band LPS consists of only shorter-chain polysaccharides . Seven hybridomas secreting A-band-specific monoclonal antibodies were produced and used to study the LPS of standard and clinical strains . Although A-band antibodies did not agglutinate any of the serotype strains presently in the International Antigenic Typing Scheme, Western immunoblots revealed that 11 of the 17 serotype strains possessed A-band LPS . In a group of 250 clinical isolates from patients with cystic fibrosis, 170 (68%) had A-band LPS on the basis of agglutination tests, but in silver-stained gels all were shown to be deficient in O-antigen-containing B band . Investigation of serial isolates from a single patient revealed a pattern of antigenic variation . During the course of the infection, serotypeable isolates became nontypeable, and the O antigen was replaced with A band as the major LPS antigen . These results suggest that A-band LPS may be the major LPS antigen in nontypeable clinical isolates and a common antigen among other P . aeruginosa strains.

Antibiot Khimioter, 1989 May, 34(5), 382 - 6
{Experimental study of antibacterial activity, therapeutic effectiveness and toxic properties of the combination of tobramycin and carbenicillin}; Vinogradova IV et al.; Tobramycin combination with carbenicillin was studied experimentally . Tobramycin is a new aminoglycoside antibiotic prepared at the Institute of New Antibiotics, the USSR Academy of Medical Sciences . It was shown that the combination had mainly synergistic action (67 per cent) on clinical strains of Pseudomonas aeruginosa which was confirmed in treatment of experimental sepsis caused by the organism . In acute experiments with albino mice there was observed summation of the general toxic action of the antibiotics used in the combination . The level and nature of the nephrotoxic action of the tobramycin combination with carbenicillin were shown in experiments with rats to be the same as those of the nephrotoxic action of tobramycin used alone . The presence of carbenicillin in the combination did not increase the inhibitory effect of tobramycin on excitement transmission in the neuromuscular synapses.

FEMS Microbiol Lett, 1989 May, 50(1-2), 51 - 3
Ultrastructural aspects of fragility of Pseudomonas aeruginosa outer membrane devoid of protein F; Gotoh N et al.; The protein F-deficient cells of Pseudomonas aeruginosa were previously found to be more susceptible to osmotic shock than the sufficient cells (Gotoh et al., J . Bacteriol., in press) . The protein F-deficient cells were observed by the thin-section method of electron microscopy to determine the effects of osmotic shock . The osmotic shock induced breakage of the protein F-deficient outer membrane, while it had no effect on the protein F-sufficient outer membrane . These results suggested that the cells lost their viability by the osmotic shock caused by fragility of the outer membrane.

FEMS Microbiol Lett, 1989 May, 50(1-2), 211 - 3
Supersusceptibility to hydrophobic antimicrobial agents and cell surface hydrophobicity in Branhamella catarrhalis; Gotoh N et al.; To clarify the cause of the supersusceptibility of Branhamella catarrhalis to macrolide antibiotics, which are well-known to be inactive to most Gram-negative bacteria, we determined its cell surface hydrophobicity by the partition experiment between water and hydrocarbons . Its cell surface was found to be markedly more hydrophobic than that of Escherichia coli or Pseudomonas aeruginosa cells . This suggested that the outer membrane of B . catarrhalis plays no role as a diffusion barrier towards hydrophobic agents.

FEMS Microbiol Lett, 1989 May, 50(1-2), 187 - 90
Evolution of Pseudomonas aeruginosa cells towards a filterable stage in seawater; Bakhrouf A et al.; In sterile nutrient-free seawater, the number of Pseudomonas aeruginosa culturable cells decreased progressively over time and the bacteria developed cells capable of passing through a 0.45 micron pore membrane . This development was more rapid in non-autoclaved, stirred seawater and the recovery of filterable cells varied depending on the membrane type used . Minicells were observed under an electron microscope . They yielded normal cells in bacteriological media with analogous colonies and an unchanged antibiotic resistance profile . Some biochemical characters, such as gelatinase or urease activity, were however modified in the filterable cells.

APMIS, 1989 May, 97(5), 475 - 8
Pseudomonas aeruginosa extracellular toxicity in infant mice and the protective effect of antitoxin A; Ogaard AR et al.; The toxin A-content of crude extracellular preparations from Pseudomonas aeruginosa has been measured by ELISA . Using infant mice as test animal, the toxicity of these preparations was evaluated . The LD 50 in infant mice was determined at 80 ng of purified toxin A in saline . With ten microliters of rabbit antitoxin A serum given together with purified toxin, the LD 50 increased to 2,500 ng . Generally there was no correlation between the LD 50 of the extracellular preparations, their quantity of toxin A as measured by ELISA, and the protective effect of antitoxin A.

J Med Microbiol, 1989 May, 29(1), 41 - 50
Adaptive resistance to aminoglycoside antibiotics in Pseudomonas aeruginosa; Gilleland LB et al.; Aminoglycoside-resistant variants of Pseudomonas aeruginosa strain PAO1 were readily selected by culturing the organism in medium containing increasing concentrations of gentamicin, tobramycin or amikacin until the strains were growing in a concentration of drug 128-fold greater than the minimal inhibitory concentration for the sensitive parent strain . These resistant strains exhibited characteristics previously associated with the impermeability type of resistance mechanism, i.e., they grew more slowly than the parent strain, the resistance was unstable in the absence of the antibiotic, and adaptation to one of the antibiotics conferred cross-resistance to other aminoglycosides . The adapted strains grew, with minimal morphological alterations, in concentrations of the various aminoglycosides that normally produced cell envelope damage, misshapen and filamentous cell formation, and cell lysis in the sensitive strain . Neither protein H1 nor phospholipid alterations appear to play a significant role in adaptive resistance to aminoglycoside antibiotics in this model system . The acquisition of adaptive resistance to the aminoglycoside antibiotics did not confer resistance to polymyxin B, another cationic antibiotic which is thought to share binding sites within the outer membrane with the aminoglycosides.

J Antibiot (Tokyo), 1989 May, 42(5), 807 - 14
L-658,310, a new injectable cephalosporin . II . In vitro and in vivo interactions between L-658,310 and various aminoglycosides or ciprofloxacin versus clinical isolates of Pseudomonas aeruginosa; Valiant ME et al.; Combinations of L-658,310 and an aminoglycoside or ciprofloxacin were tested against clinical isolates of Pseudomonas aeruginosa using a checkerboard broth dilution technique . Using the mean fractional bactericidal concentration of less than or equal to 0.5 as the criterion for synergy, the combinations L-658,310/tobramycin and L-658,310/ciprofloxacin against strains of P . aeruginosa resistant to the companion drug were synergistic . The data plotted as isobolograms showed synergy for all combinations tested . Synergy was clearly demonstrated in time-kill experiments . A greater than 3-log decrease in viable cell count for P . aeruginosa was seen after exposure for 24 hours to subinhibitory concentrations of the combined agents . In in vivo mouse models, the efficacy of L-658,310 against experimental P . aeruginosa bacteremias was enhanced by the addition of a low dose of an aminoglycoside to the treatment regimen, thus confirming the synergy demonstrated in time-kill experiments.

J Antibiot (Tokyo), 1989 May, 42(5), 662 - 6
Mureidomycins A-D, novel peptidylnucleoside antibiotics with spheroplast forming activity . I . Taxonomy, fermentation, isolation and physico-chemical properties; Inukai M et al.; A strain of actinomycetes identified as Streptomyces flavidovirens produced new antibiotics, mureidomycins (MRD's) A approximately D, specifically active against Pseudomonas aeruginosa . They were isolated from the culture filtrate by successive column chromatographies such as Amberlite XAD-2 and CG-50, Whatman DE-52 and Toyopearl HW-40 . They were amphoteric white powders and soluble in methanol and water . Their molecular weights and molecular formulae in parentheses were 840 (C38H48N8O12S), 842 (C38H50N12S), 897 (C40H51N9O13S) and 899 (C40H53N9O13S), respectively . m-Tyrosine and two unknown substances were detected by amino acid analyses as their common constituents . MRD's A and C contained uracil but MRD's B and D dihydrouracil instead of uracil.

J Bacteriol, 1989 May, 171(5), 2599 - 604
Localization of the control region for expression of exotoxin A in Pseudomonas aeruginosa; Tsaur ML et al.; The 2,760-base-pair (bp) PstI-EcoRI segment of the chromosome of Pseudomonas aeruginosa PA103 which carries the exotoxin A structural gene was expressed from an internal promoter when cloned in a pUC9 derivative and transformed into a nontoxigenic mutant of P . aeruginosa PAO1 . The unique terminal EcoRI site was deleted, and a new EcoRI site was substituted for a PvuI site located 107 bp 5' to the transcription initiation site . Following EcoRI cleavage, Bal31 deletions were generated from this site, and an EcoRI linker sequence, GGAATTCC, was inserted in place of the deleted DNA . Mutants with deletions located 73 bp or more upstream of the transcription initiation site retained normal expression, whereas in mutants with deletions extending into the region 69 bp or less upstream of this site, exotoxin synthesis was greatly reduced . From a KpnI site located 473 bp 3' to the transcription initiation site, a similar series of Bal31 deletion mutants were generated in which the inserted EcoRI linker sequence was located within the same 72-bp region . Pairs of mutants from the two deletion series were identified in which the EcoRI linker was located at the same sequence, and these mutant pairs were ligated to derive a series of constructs in which the EcoRI linker sequence GGAATTCC was substituted for an 8-bp sequence within the 72-bp region . Some of these linker-substituted mutants showed greatly reduced exotoxin A synthesis . The results are consistent with a binding site for a positive activator contiguous with the binding site for an RNA polymerase.

J Bacteriol, 1989 May, 171(5), 2312 - 7
High osmolarity is a signal for enhanced algD transcription in mucoid and nonmucoid Pseudomonas aeruginosa strains; Berry A et al.; Chronic lung infection with mucoid, alginate-producing strains of Pseudomonas aeruginosa is a major cause of mortality in cystic fibrosis (CF) patients . Transcriptional activation of the P . aeruginosa algD gene, which encodes GDPmannose dehydrogenase, is essential for alginate synthesis . Activation of algD is dependent on the product of the algR gene . Sequence homology between the P . aeruginosa algR gene and the Escherichia coli ompR gene, which regulates the cellular response to changes in osmolarity of the growth medium, together with the abnormally high levels of Na+ and Cl- in respiratory tract fluid in CF patients suggested that high osmolarity in the lung of the CF patient might be a signal contributing to the induction of alginate synthesis (mucoidy) in infecting P . aeruginosa . In both mucoid and nonmucoid P . aeruginosa strains (containing a functional algR gene), transcriptional activation of algD increased as the osmolarity of the culture medium increased . The increased activation of algD at high osmolarity was not in itself sufficient to induce alginate synthesis in nonmucoid strains, however, suggesting that other environmental factors are involved in full activation of the alginate genes . The targets of AlgR and OmpR, the algD promoter and the ompC and ompF promoters, respectively, were found to have appreciable sequence homology in the -60 to -110 regions . In E . coli, OmpR was capable of activating the algD promoter nearly as well as AlgR, but in both cases, activation occurred only under conditions of high osmolarity.

J Bacteriol, 1989 May, 171(5), 2287 - 92
Genetic comparison of bacteriophage PS17 and Pseudomonas aeruginosa R-type pyocin; Shinomiya T et al.; PS17 is a bacteriophage of Pseudomonas aeruginosa that is serologically cross-reactive with phage tail-like bacteriocins called R-type pyocins . In addition to having immunological cross-reactivity, certain genes are functionally complementable between PS17 and R-type pyocins . To compare the genetic structures of PS17 and R-type pyocins, a physical map of PS17 genes was constructed by cloning phage DNA fragments on RSF1010-derived vector plasmids . The head and tail gene clusters were tandemly arrayed and together occupied about half of the 41-kilobase-pair PS17 chromosome . With use of these phage clones, the following results were obtained with respect to the genetic relationship between PS17 and R-type pyocins: (i) serological cross-reaction between PS17 and pyocin occurred for the major sheath protein and two components of the fiber, (ii) a certain pyocin mutation was complemented by cloned phage fragments, and (iii) the phage DNA fragment carrying sheath and core tube genes was shown to hybridize to the DNA fragment carrying the pyocin R2 genes.

Infect Immun, 1989 May, 57(5), 1369 - 73
Mutations in the hemolytic-phospholipase C operon result in decreased virulence of Pseudomonas aeruginosa PAO1 grown under phosphate-limiting conditions; Ostroff RM et al.; The phospholipase C (PLC) operon of Pseudomonas aeruginosa consists of plcS, which encodes a heat-labile secreted hemolysin, and two in-phase, overlapping genes, plcR1 and plcR2, which may encode Pi-regulatory genes . A 2.8-kilobase-pair deletion mutation in this operon was constructed, and a tetracycline resistance (Tcr) cartridge replaced the deleted sequences . A deletion mutant of strain PAO1 was obtained through recombination between the flanking regions of the mutated cloned PLC operon and the homologous chromosomal regions . The deletion of the chromosomal PLC operon and its replacement by the Tcr cartridge was confirmed by Southern hybridization . The deletion strain, PLC SR, is nonhemolytic . However, it retains PLC activity when measured on a synthetic substrate . A second mutant strain, PLC R, contains a deletion in the plcR genes . This mutant is more hemolytic and produces more enzymatic activity than PAO1 . The virulence of both of these mutants was compared with that of PAO1 in the mouse burn model of infection . When mice were infected with cultures grown in a high-Pi medium, there was a 10-fold increase in the 50% lethal dose of the mutants compared with PAO1 . In contrast, when the inoculum originated from low-Pi cultures, there was a 200- to 10,000-fold increase in the 50% lethal dose of the mutants over PAO1.

Biochim Biophys Acta, 1989 May 1, 995(3), 285 - 90
Elastolytic activity of Pseudomonas aeruginosa elastase; Saulnier JM et al.; Elastolysis of insoluble elastin by Pseudomonas aeruginosa elastase was found to be less specific (higher apparent Km value) but more active (higher activity) than with pancreatic elastase . Furthermore, pancreatic and P . aeruginosa elastases act synergistically during the initial stages of elastolysis . After extensive hydrolysis, the size distribution of digestion products was lower with P . aeruginosa than with pancreatic elastase . The higher extent of hydrolysis may be explained by the fact that, if pancreatic elastase needs at least six sub-sites for activity, P . aeruginosa elastase may hydrolyse tetrapeptides such as tetraalanine, or synthetic substrates such as furylacryloyltripeptides FA-X-Leu-Y, X and Y being Gly and/or Ala.

Proc Natl Acad Sci U S A, 1989 May, 86(9), 3075 - 9
Identification of amino acid residues essential for the enzymatic activities of pertussis toxin; Locht C et al.; The enzymatic ADP-ribosyltransferase activity associated with the S1 subunit of pertussis toxin is considered to be responsible for its biological effects . Although pertussis toxin has no significant homology to other ADP-ribosylating toxins such as diphtheria toxin and Pseudomonas aeruginosa exotoxin A, the results presented in this paper show that, as for diphtheria toxin and exotoxin A, tryptophan and glutamic acid residues are essential for the enzymatic activities of pertussis toxin . Moreover, a structural motif can be identified around the critical glutamic acid residue . Chemical modification or site-directed deletion or replacement of Trp-26 abolishes ADP-ribosyltransferase and the associated NAD glycohydrolase activities . Both enzymatic activities are also abolished when Glu-129 is deleted or replaced by aspartic acid . Mutations at the Glu-106 position do not significantly reduce the enzymatic activities of the S1 subunit . The mutations do not affect the ability of the different S1 forms to be recognized by a variety of monoclonal antibodies, including neutralizing antibodies . Pertussis toxin containing a deletion or replacement of Trp-26, Glu-129, or both in the S1 subunit should thus be devoid of toxic activities without losing its reactivity with protective antibodies and, therefore, could be safely included in new generation vaccines against whooping cough.

Gene, 1989 Apr 30, 77(2), 205 - 10
Construction of broad-host-range vectors for general cloning and promoter selection in Pseudomonas and Escherichia coli; Farinha MA et al.; We have constructed two promoter-selection vectors based upon the broad-host-range plasmid pRO1614 . pQF40 (6 kb) contains a promoterless tetA gene downstream from a large multiple cloning site while pQF26 (5.4 kb) possesses a promoterless cat cartridge . The latter vector displayed a copy number of 13 in Pseudomonas aeruginosa and 39 in Escherichia coli . When promoter sequences derived from the Pseudomonas phage phi PLS27 were cloned into pQF26, high levels of chloramphenicol-acetyltransferase were detected in P . aeruginosa . In E . coli the activity was approximately one-third that in P . aeruginosa when corrections were made for the plasmid copy number.

J Biol Chem, 1989 Apr 15, 264(11), 6297 - 301
Identification of porins in the outer membrane of Pseudomonas aeruginosa that form small diffusion pores; Yoshihara E et al.; The purified outer membrane proteins of Pseudomonas aeruginosa were reconstituted with phosphatidylcholine and dicetylphosphate into membrane vesicles, and these were tested by the liposome swelling method for the diffusion of saccharides with different Mr . Proteins C (Mr, 70,000), D (Mr, 46,000), and E (Mr, 43,000) were found to confer the monosaccharide-permeable pores in the reconstituted liposome membranes . The membrane vesicles containing proteins F (Mr, 34,000), G (Mr, 25,000), or H (Mr, 19,000) showed no detectable pore-forming activity . The pores formed by proteins C, D, or E appeared to be smaller than that formed by the Escherichia coli porins . The size of the solutes that permeated through the newly identified porins is similar to that through the intact and purified outer membrane of P . aeruginosa (Yoneyama, H., and Nakae, T . (1986) Eur . J . Biochem . 157, 33-38; Yoshihara, E., Gotoh, N., and Nakae, T . (1988) Biochem . Biophys . Res . Commun . 156, 470-476).

Am Rev Respir Dis, 1989 Apr, 139(4), 877 - 84
Nosocomial pneumonia in patients receiving continuous mechanical ventilation . Prospective analysis of 52 episodes with use of a protected specimen brush and quantitative culture techniques; Fagon JY et al.; Epidemiologic studies of nosocomial bacterial pneumonia in patients requiring mechanical ventilation have been limited because of the poor reliability of diagnosis procedures in this setting . To determine prognostic and descriptive factors of ventilator-associated (V-A) pneumonia, we prospectively studied 567 patients who had been receiving mechanical ventilation for more than 3 days in our unit . Fiberoptic bronchoscopy using a protected specimen brush (PSB) was performed on each patient suspected of having pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions . The diagnosis of V-A pneumonia was retained only if PSB specimens yielded greater than 10(3) cfu/ml of at least one microorganism, unless this result was established to be a false positive result on follow-up . V-A pneumonia developed in 49 patients for a total of 52 episodes (9%) . The actuarial risk of V-A pneumonia was 6.5% at 10 days, 19% at 20 days, and 28% at 30 days of ventilation . Patients with pneumonia were significantly older (65 versus 57 yr of age, p less than 0.01) and more frequently had severe underlying illnesses (24 versus 10%, p less than 0.01) than did patients without pneumonia . A total of 84 microorganisms (51 gram-negative and 33 gram-positive) were isolated in significant concentrations from PSB specimens . Pseudomonas aeruginosa and Staphylococcus aureus were involved in 31 and 33% of these pneumonias, respectively . Forty percent of all specimens yielded a polymicrobial flora with more than one potential pathogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Clin Orthop, 1989 Apr, (241), 209 - 12
Arthroscopy in acute septic knees . Management in pediatric patients; Stanitski CL et al.; Arthroscopic evacuation, debridement, and irrigation of acute septic knees in children were effective adjuncts in the treatment of this joint infection . Sixteen knees in 16 pediatric patients were treated with arthroscopic management . Ninety-four percent of the knees had sepsis secondary to Staphylococcus aureus . Two immune-suppressed patients (postrenal transplants) had combined S . aureus and Pseudomonas aeruginosa infections . Twenty-five percent of the patients had a foreign body in the joint that was removed arthroscopically . No postoperative irrigation or drainage systems were used . At an average follow-up period of three years, no evidence of persistent or recurrent infection was noted . Roentgenograms showed no evidence of joint or epiphyseal destruction . Because of the low morbidity associated with the procedure, rapid restoration of joint motion and patient mobility was seen in all patients . Arthroscopic debridement of acute septic knees may be carried out in pediatric patients, given appropriate equipment and arthroscopic skills.

Riv Eur Sci Med Farmacol, 1989 Apr, 11(2), 143 - 8
{Pseudomonas aeruginosa infection of the sternum and costal cartilages in cardiosurgery . Therapeutic experience using aztreonam}; Donegani E et al.; Clinical effectiveness of Aztreonam was studied . This new monobactam antimicrobial agent was tasted in the treatment of post-operative infectious complications of cardiac surgical sternal wounds . Ten patients (4 men and 6 women, age range 20 to 68 years) were entered into the study . All had a Pseudomonas aeruginosa infection of sternum or sternum and ribs and all underwent an extensive regional surgery of the infection wound and received a topical and/or IV treatment with Aztreonam . In all cases we obtained a satisfactory result, with complete eradication of the infection . Both local and systemic tolerance to the drug were excellent and no side-effect was registered . Therefore Aztreonam can be considered an active and safe antibiotic for the treatment of sternal and/or costal postsurgical infections by Pseudomonas aeruginosa.

Can J Microbiol, 1989 Apr, 35(4), 520 - 3
Iodine sensitivity of bacteria isolated from iodinated water systems; Pyle BH et al.; Fourteen bacterial isolates, predominantly Pseudomonas sp., from two water systems disinfected by iodinated anion-exchange resins were studied and compared with an isolate of Pseudomonas aeruginosa from a povidone-iodine solution and four other isolates . Pseudomonas cepacia and P . aeruginosa grown in brain heart infusion were 3 to 5 logs less sensitive to 1 mg/L I2 (pH 7.2, 1 min) when compared with cultures grown in phosphate buffer . Another P . cepacia isolate was the least sensitive culture when grown in brain heart infusion (1 log decrease) but was more sensitive after cultivation in phosphate buffer (5 logs) . Isolates from an iodinated potable water system, including P . cepacia, Staphyloccus warneri, and a Bacillus sp., were all less sensitive to iodine than a "resistant" P . aeruginosa and three other isolates when grown in brain heart infusion . A clinical isolate of P . aeruginosa exhibited intermediate sensitivity . The sensitivity of bacteria to iodine is thus highly variable, depending on the organism as well as the growth conditions.

Ann Pediatr (Paris), 1989 Apr, 36(4), 275 - 8
{Arthropathies following the administration of pefloxacin to an adolescent with mucoviscidosis}; Kesseler A et al.; We report the occurrence of knee joint effusion with prolonged functional impairment in a 17-year old boy with cystic fibrosis treated with pefloxacin for recurrent lower respiratory tract infections caused by Pseudomonas aeruginosa . Because the quinolone pefloxacin fairly often induces joint disease in pediatric age groups, we advocate restricting its use to those patients whose growth is completed . In growing individuals, it seems reasonable to use second generation quinolones only in infections caused by resistant organisms and to avoid exerting the joints during treatment.

Burns, 1989 Apr, 15(2), 117 - 9
Burn wound infection in 100 patients treated in the burn unit at Jordan University Hospital; Karyoute SM; A retrospective chart review was conducted for 100 patients treated in our Burn Unit to study the incidence and nature of burn wound infection, which is our most common and serious complication in burns . Quantitative estimates of infection were obtained by culturing bacterial flora from surface swabs . Pseudomonas aeruginosa was the predominant burn wound pathogen, only a few patients developed fungal infections . A significant association was found between increasing burn size and increasing incidence of Gram-negative invasive organisms . Restriction in the prophylactic usage of antibiotics and environmental control within the Burn Unit may help to decrease the incidence of infection . Regular wound care has been effective in decreasing wound sepsis . It has been concluded that the relatively poor socioeconomic conditions of many of our patients and the delay in referring patients to the Burn Unit are the most important predisposing factors in burn wound infection.

J Antimicrob Chemother, 1989 Apr, 23 Suppl D, 47 - 54
Cefmetazole treatment of intra-abdominal infection; Holloway WJ et al.; Seventy-nine patients were enrolled in a study comparing cefmetazole and cefoxitin as single agent antibiotic therapy for intra-abdominal infection . Thirty-seven patients had appendicitis, 16 patients had perforated peptic ulcer while 26 patients had a variety of other infectious processes . The clinical response to both antibiotics was good and tolerance was equivalent . Four patients with Pseudomonas aeruginosa isolated from the initial culture experienced microbiological failure . Three patients treated with cefmetazole had prolongation of the prothrombin time.

J Hosp Infect, 1989 Apr, 13(3), 231 - 9
A comparison of hypochlorite and phenolic disinfectants for disinfection of clean and soiled surfaces and blood spillages; Bloomfield SF et al.; Suspension test methods were used to compare phenolic and hypochlorite disinfectants under conditions as recommended for use in hospitals . Using plasma to simulate soiled conditions, Clearsol (1% v/v) and Stericol (2% v/v) produced satisfactory disinfection, (i.e . 5 log reduction in 5 mins against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa in the presence of up to 50% v/v plasma (25 mg ml-1 plasma protein) . Although sodium dichloroisocyanurate (NaDCC) at 2500 ppm AvCl2 was effective in the presence of up to 20% plasma, compared to 10% plasma for sodium hypochlorite 2500 ppm, sensitivity of NaDCC to inactivation was greater than for phenolics . In the presence of blood, both hypochlorites and phenolics were substantially inactivated, although here the effectiveness of NaDCC at 10,000 ppm was equivalent to the phenolics . Our results indicate that hypochlorites at 10,000 ppm, Clearsol 1% and Stericol 2% may be ineffective for treatment of blood spills unless applied at v:v ratios of 9 parts disinfectant to 1 part blood . In this situation, chlorine-releasing powder formulations, which produce higher AvCl2 concentrations and contain spilled material, offer an effective alternative.

Ann Otol Rhinol Laryngol, 1989 Apr, 98(4 Pt 1), 293 - 7
Quantitative bacterial cultures and beta-lactamase activity in chronic suppurative otitis media; Brook I et al.; Aspiration of the exudate through open perforation was performed in 54 children with chronic suppurative otitis media . Eighty aerobic and 81 anaerobic isolates were recovered . Aerobic bacteria only were involved in 20 patients (37%), and anaerobic organisms only in seven (13%) . Mixed aerobic and anaerobic isolates were recovered from 27 patients (50%) . The most common bacteria isolated were anaerobic gram-positive cocci, Bacteroides melaninogenicus group, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus . There were 45 beta-lactamase-producing bacteria (BLPB), 30 aerobes, and 15 anaerobes recovered from 38 patients (70%) . beta-Lactamase activity was detected in 30 of the 38 ear aspirates (79%) that contained BLPB . All but one of these organisms were in excess of 10(4) colony-forming units/mL . The detection of beta-lactamase activity in the ear aspirates provides evidence of the role of BLPB in the failure of penicillin therapy to eradicate chronic ear infection.

J Bacteriol, 1989 Apr, 171(4), 2142 - 7
Assembly of mutant pilins in Pseudomonas aeruginosa: formation of pili composed of heterologous subunits; Pasloske BL et al.; Recently, we reported the degree of N-terminal processing within the cytoplasmic membranes of three mutant pilins from Pseudomonas aeruginosa PAK with respect to leader peptide removal and the methylation of the N-terminal phenylalanine (B . L . Pasloske and W . Paranchych, Mol . Microbiol . 2:489-495, 1988) . The results of those experiments showed that the deletion of 4 or 8 amino acids within the highly conserved N terminus greatly inhibited leader peptide removal . On the other hand, the mutation of the glutamate at position 5 to a lysine permitted leader peptide cleavage but inhibited transmethylase activity . In this report, we have examined the effects of these mutant pilins upon pilus assembly in a P . aeruginosa PAO host with or without the chromosomally encoded pilin gene present . Pilins with deletions of 4 or 8 amino acids in the N-terminal region were not incorporated into pili . Interestingly, pilin subunits containing the glutamate-to-lysine mutation were incorporated into compound pili together with PAO wild-type subunits . However, the mutant pilins were unable to polymerize as a homopolymer . When wild-type PAK and PAO pilin subunits were expressed in the same bacterial strain, the pilin subunits assembled into homopolymeric pili containing one or the other type of subunit.

J Gen Microbiol, 1989 Apr, 135 ( Pt 4), 817 - 23
Positive control of Pseudomonas aeruginosa amidase synthesis is mediated by a transcription anti-termination mechanism; Drew R et al.; The DNA sequence of the region upstream from the amidase structural gene (amiE) of Pseudomonas aeruginosa indicates that amidase (EC 3.5.1.4) is transcribed from an Escherichia coli-like promoter located 150 bp before the amiE translation initiation codon . The sequence between the promoter and the coding sequence includes a single open reading frame followed by an E . coli-like rho-independent transcription terminator . A deletion within the presumed terminator region which disrupts the potential stem/loop formation leads to high constitutive amidase expression which is independent of the product of the regulator gene (amiR) . It is proposed that the catabolic aliphatic amidase of P . aeruginosa is regulated by a transcription anti-termination mechanism . The magnoconstitutive mutant PAC433 has promoter and terminator sequences identical to the wild-type PAC1 but contains a single base pair change in the amiE gene ribosome-binding site.

Chin Med J (Engl), 1989 Apr, 102(4), 313 - 8
Study of in vitro antibacterial activity of 19 antimicrobial agents against Pseudomonas aeruginosa; Wang R et al.; The in vitro antibacterial activity of 19 antimicrobial agents against 40 strains of P aeruginosa was studied . The 19 antimicrobial agents included 7 semisynthetic penicillins, 6 third generation cephalosporins, 5 aminoglycosides and 1 quinolone agent . The minimal inhibition concentrations (MIGs) were measured by the serial dilution on solid agar . Ceftazidime was the most active in 19 antimicrobial agents again P aeruginosa (MIC50: 1 microgram/ml, MIC90: 2 micrograms/ml) Amikacin and ofloxaxin followed it in activity . Acylureido-penicillins, such as azlocillin, furbenicillin and piperacillin were highly active against P aeruginosa, which could inhibit, 92.5%, 90% and 85% of these strains at a concentration of 8 micrograms/ml . Cefsulodine and cefoperazone were also active against the same strains, inhibiting 92.5% and 99% of the strains at a concentration of 8 micrograms/ml . The potency of the agents mentioned above against P . aeruginosa was similar to that of aminoglycosides . The drug susceptibility of 10 strains isolated in our hospital was compared with that of 29 strains of other hospitals in Beijing . The MICS of 5 penicillins and 3 cephalosporins against the isolates of our hospital was higher than that of other hospitals, suggesting that the susceptibility of beta-lactam antibiotics against isolates of our hospital was lower . The effects of combined use of azlocillin with oxacillin and piperacillin with ofloxacin against 4 strains of carbenicillin-resistant P aeruginosa was studied using check-board testing . The synergy and partial synergy were observed in both combinations.

Zhonghua Jie He He Hu Xi Za Zhi, 1989 Apr, 12(2), 82 - 5, 126
{Latent risk and precautions against cross infection at the respiratory disease unit}; Yu GH; To investigate the contamination of respiratory pathogens in the ward of respiratory disease, bacterial count was conducted in air of different rooms of the ward . It was found that the air total bacterial count was much higher in the nursing room and ICU than that in the rooms with good ventilation (P less than 0.01) . Pathogens were examined in the saliva of the medical staff . No significant difference was found in the pathogens of the saliva between the COPD patients and medical staff, who were considered as bacteria-carriers . 155 times of bacteriologic examinations were made in 68 humidified bottles for oxygen supplement . All bottles had a mixed contamination, with Pseudomonas aeruginosa being one of common pathogens.

FEMS Microbiol Lett, 1989 Apr, 49(2-3), 259 - 62
Effect of iron concentration and growth rate on the expression of protein G in Pseudomonas aeruginosa; Yates JM et al.; Protein G of Pseudomonas aeruginosa was found to be strongly induced by iron and repressed by iron restriction in chemically defined medium (CDM) . Expression in batch culture was influenced by phase of growth and in iron limited continuous culture by the doubling time . We suggest that protein G may constitute a low-affinity iron uptake system.

Can J Microbiol, 1989 Apr, 35(4), 511 - 4
The use of Tween 20 in a sensitive turbidimetric assay of lipolytic enzymes; von Tigerstrom RG et al.; A turbidimetric esterase assay was developed using a Tween 20 solution in the presence of CaCl2 and Lysobacter enzymogenes esterase (EC 3.1.1.1) as the enzyme source . The reaction was followed by measuring the increase in the optical density at 500 nm (OD500) due to the hydrolytic release of the fatty acids from Tween 20 and their precipitation as the calcium salts . Concentrations of 1.8% Tween and 3 mM CaCl2 were found to be optimal for the assay of 0.036 to 0.15 esterase units in a 4-mL reaction mixture over a 30-min period . The esterase reactions were linear with time at least up to 1.2 OD500 and the rate of increase in the OD500 was proportional to the enzyme concentration . Low initial reaction rates were seen with low esterase activity, presumably because of the limited solubility of the fatty acid - calcium salt in a 1.8% Tween solution . This turbidimetric method is much simpler and at least 36 times more sensitive than the titrimetric assay with Tween 20, and at least four times more sensitive than a spectrophotometric assay with p-nitrophenyl palmitate . This assay has been used to determine the activities of cell-associated and excreted esterases produced by Lysobacter enzymogenes and Pseudomonas aeruginosa, and of lipolytic enzymes from porcine liver, Chromobacterium viscosum, Candida cylindracea, and wheat germ.

Zentralbl Bakteriol Mikrobiol Hyg {B}, 1989 Apr, 187(4-6), 337 - 64
{The significance of the contamination of dental care articles . The results of a field study}; Hingst V; Permissible conclusions both from recent available literature and our own field-study results concerning the problematic nature of microbial contamination of dental hygiene articles and the resulting possible health hazard for the consumer can be summarized as follows: Manufacturing practices as are given in the basic instructions for production sites of the cosmetic industry, render a possible degree of microbial contamination . This largely rules out the danger of infection of the consumer upon acquisition of the dental hygiene product . Secondary contamination of these products, as inevitably is the case during use of dental hygiene articles, leads to microbial colonization especially of toothbrush bristles . The extent of this colonization depends at least partially upon the utilization age of the toothbrush . Also for this reason a toothbrush should be replaced by a new one after period of three months, six months at the latest and in all cases of inflammatory changes of the mouth and throat region . The contamination of both the glass or plastic container used for rinsing the teeth after brushing or for gargling can be held within certain limits by dry storage . Only in exceptional cases do mouthwashes show a small degree of contamination . Provided they contain antimicrobial substances, no therapeutically serviceable possibilities worth mentioning follow for the reduction of oropharyngeal flora . Microbial colonization of toothpastes as a result of secondary contamination following use is observed only in exceptional cases due to their preservative content . Significant germination of stagnated residual water in waterpicks often occurs, achieving germ counts up to more than 10(7) cfu per ml . Moreover, waterpicks can represent a biotope for Pseudomonas aeruginosa, and should be used neither by patients with open wounds or mucous membrane lesions in the oropharyngeal area, nor by patients with reduced immune resistance . Manufacturers of waterpicks are urged to impede or prevent the stagnation of residual water more effectively by introducing constructive improvements . Denture and retainer cleansing agents presently on the market display a sufficient antimicrobial effect within the frame of their application, however do not meet the standards set for disinfectants . Dental hygiene products are without relevance for the epidemiology of Legionnaires' disease.

Zh Mikrobiol Epidemiol Immunobiol, 1989 Apr, (4), 64 - 8
{Isolation of Pseudomonas aeruginosa exotoxin A by affinity chromatography using specific antibodies}; Vovk VA et al.; The method for the isolation of specific antibodies to P . aeruginosa exotoxin A from rabbit antitoxic serum by means of affinity chromatography has been developed . The conditions permitting the isolation of immunoglobulins to exotoxin A, practically without losses, have been experimentally established . The method for the isolation of exotoxin A from P . aeruginosa culture fluid with the use of specific antibodies to exotoxin A, immobilized on Sepharose 4B, has been worked out . This method makes it possible to obtain 21 mg of exotoxin A per cycle in a column having a working capacity of 25 ml, the yield being 87% of exotoxin A from its initial content in acellular culture fluid . The preparation of exotoxin A thus obtained is toxic, homogeneous and has specific enzymatic activity . Its molecular weight is 71 KD.

Antimicrob Agents Chemother, 1989 Apr, 33(4), 526 - 8
Changing susceptibility of Pseudomonas aeruginosa isolates from cystic fibrosis patients with the clinical use of newer antibiotics; Bosso JA et al.; To detect a change in antibiotic susceptibility patterns in Pseudomonas aeruginosa isolates upon the introduction and clinical use of ciprofloxacin, aztreonam, and ceftazidime, MICs for clinical isolates collected before introduction of the antibiotics, during early clinical use, and later were determined for these and seven other antipseudomonal antibiotics . Concomitant resistance to two or more antibiotics was also studied . Over the three study periods, rates of susceptibility to 9 of the 10 antibiotics decreased . The largest decrease occurred with ceftazidime . Analysis of subsets of isolates from patients treated with ciprofloxacin or aztreonam also showed declining susceptibility to the latter but a stabilization of susceptibility to the former after an initial decline . Concomitant resistance within and among antibiotic classes was common.

J Clin Microbiol, 1989 Apr, 27(4), 691 - 9
Purification, characterization, and immunological cross-reactivity of alginates produced by mucoid Pseudomonas aeruginosa from patients with cystic fibrosis; Pedersen SS et al.; Alginates from nine mucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis were purified by repeated ethanol precipitation, nuclease digestion, anion-exchange chromatography, dialysis, and lyophilization . Uronic acid constituted 72% of the dry weight when mannuronolactone was used as the internal standard in the carbazole-borate assay for uronic acids . The average degree of acetylation was 16%, and the ratio of mannuronic acid to gluluronic acid was 4.7 . No homopolymeric blocks of guluronic acid were found when analyzed by nuclear magnetic resonance spectroscopy . Contaminating proteins were denatured by heating, and during purification the content of protein relative to alginate fell from 566 to 0.9% . The content of lipopolysaccharide was 0.012% . No immunological or biological activity was attributable to the protein or lipopolysaccharide content as estimated by immunoblotting, enzyme-linked immunosorbent assay (ELISA), and a neutrophil chemotaxis assay . Rabbits were hyperimmunized with P . aeruginosa alginates and alginate from the seaweed Laminaria hyperborea, and an ELISA that detected alginate-specific antibodies was developed . Antibodies to P . aeruginosa alginate were detected by ELISA in 1:4,000 dilutions of serum from patients with cystic fibrosis with chronic P . aeruginosa lung infection . The serological cross-reactions between serum from the nine patients with cystic fibrosis and the corresponding P . aeruginosa alginates were investigated and showed considerable heterogeneity . This finding indicates that P . aeruginosa alginate from more than one P . aeruginosa strain should be used in serological tests . There was no serological cross-reactivity between P . aeruginosa and Laminaria hyperborea alginate in either rabbits or patients with cystic fibrosis.

J Antibiot (Tokyo), 1989 Apr, 42(4), 598 - 603
Structure activity relationships in PIPC-analogues against Pseudomonas aeruginosa; Mitsuyama J et al.; The relationship between the chemical structure and mode of action of piperacillin-analogues (PIPC-analogues) against Pseudomonas aeruginosa was investigated . The antibacterial activities of PIPC-analogues became stronger as the chain length of the alkyl group on the N-4 position in 2,3-dioxopiperazine when tested in constitutively beta-lactamase-producing strain, but not paralleled in wild and beta-lactamase-less strains . The outer membrane permeability was hardly affected by the chain length of the alkyl group at the N-4 position . The stability to beta-lactamase was stronger with the increase of the number of the carbon atoms of N-4 position . In the binding-affinities to the lethal penicillin-binding proteins (PBPs), compounds PIPC (C-2), C-3 and C-4 showed lower ID50 values than compounds C-1, C-6 and C-8 . These results suggested that the stability to beta-lactamase was the governing part for the antibacterial activity in constitutively beta-lactamase-producing strain, and the binding affinity to lethal PBPs directly contributed to the antibacterial activity in wild and beta-lactamase-less strains.

J Antibiot (Tokyo), 1989 Apr, 42(4), 527 - 32
Coumamidines, new broad spectrum antibiotics of the cinodine type . I . Discovery, taxonomy of the producing organism and fermentation; Jackson M et al.; Coumamidines are water-soluble basic antibiotics related to the glycocinnamoylspermidines . They are produced by a soil isolate designated Saccharopolyspora sp . AB 1167L-65 . The coumamidines have broad spectrum activity and were selected in a screen for substances which inhibit Pseudomonas aeruginosa.

J Antibiot (Tokyo), 1989 Apr, 42(4), 512 - 20
Pacidamycins, a novel series of antibiotics with anti-Pseudomonas aeruginosa activity . II . Isolation and structural elucidation; Chen RH et al.; A novel class of antibiotics was isolated from cultures of Streptomyces coeruleorubidus strain AB 1183F-64 . The antimicrobial activity of the pacidamycins is selective against Pseudomonas aeruginosa . The various congeners are nucleoside peptides which differ in the terminal amino acid residues . The structures were determined using MS-MS and 2D NMR techniques.

J Antibiot (Tokyo), 1989 Apr, 42(4), 506 - 11
Pacidamycins, a novel series of antibiotics with anti-Pseudomonas aeruginosa activity . I . Taxonomy of the producing organism and fermentation; Karwowski JP et al.; The pacidamycins are a new complex of nucleosidyl-peptide antibiotics with highly specific activity against Pseudomonas aeruginosa . They are produced by Streptomyces coeruleorubidus AB 1183F-64 which was isolated from a soil sample collected at Offenburg in the FRG . The mature spore masses of the producing organism are greenish gray to blue, and the spore chains are arranged in spirals . After the structures of the pacidamycins were determined, the fermentation medium was supplemented with component amino acids . This resulted in the directed biosynthesis of several members of the complex . The overall antibiotic recovered was increased from 1 approximately 2 mg/liter to more than 100 mg/liter through a combination of strain selection, medium manipulation and amino acid feeding experiments.

J Allergy Clin Immunol, 1989 Apr, 83(4), 735 - 7
Successful use of aztreonam in a patient who failed oral penicillin desensitization; Loria RC et al.; A 69-year-old woman with Pseudomonas aeruginosa sepsis developed wheezing during the course of an oral penicillin desensitization . Despite treatment of the bronchospasm and readministration of the same dose of phenoxymethyl penicillin, wheezing recurred requiring stopping the desensitization procedure . Aztreonam, a monobactam antibiotic with activity against aerobic gram-negative bacilli, was administered along with an aminoglycoside . The patient tolerated a full course of aztreonam with no adverse reactions . This case report supports previous in vitro and in vivo studies, suggesting that aztreonam does not cross-react with penicillin-specific antibodies and that it may be well tolerated in beta-lactam-allergic individuals.

J Bacteriol, 1989 Apr, 171(4), 2244 - 8
Analysis of a common-antigen lipopolysaccharide from Pseudomonas aeruginosa; Rivera M et al.; Lipopolysaccharide isolated from Pseudomonas aeruginosa PAO1 (O5 serotype) was separated into two antigenically distinct fractions . A minor fraction, containing shorter polysaccharide chains, reacted with a monoclonal antibody to a P . aeruginosa common antigen but did not react with antibodies specific to O5-serotype lipopolysaccharide . In contrast, fractions containing long polysaccharide chains reacted only with the O5-specific monoclonal antibodies . The shorter, common-antigen fraction lacked phosphate and contained stoichiometric amounts of sulfate, and the fatty acid composition of this fraction was similar to that of the O-antigen-specific fraction . The lipid A derived from the serotype-specific lipopolysaccharide cross-reacted with monoclonal antibodies against lipid A from Escherichia coli, while the lipid A derived from the common antigen did not react . We propose that many serotypes of P . aeruginosa produce two chemically and antigenically distinct lipopolysaccharide molecules, one of which is a common antigen with a short polysaccharide and a unique core-lipid A structure.

J Bacteriol, 1989 Apr, 171(4), 1817 - 24
Regions of toxin A involved in toxin A excretion in Pseudomonas aeruginosa; Hamood AN et al.; Toxin A is excreted by Pseudomonas aeruginosa as a mature 66,583-dalton protein . In this study, we used molecular cloning and deletion analysis to define specific regions of the toxin molecule involved in its excretion . Subclones that express either the amino terminus, the carboxy terminus, or toxin A molecules with internal deletions were constructed . The hypotoxigenic mutant PAO-T1 was used as a host for the expression of the toxin constructs . When overexpressed (by the presence of extra copies of the toxin A-positive regulatory gene, regA, in trans), toxin A-cross-reactive materials produced by most of these constructs were detected in the supernatant of PAO-T1 . The supernatant of P . aeruginosa PAO-T1 contained proteolytic activity that degraded toxin A-derived products but not the intact toxin molecule . A single SalI intragenic deletion (coding for the leader peptide, the first 30 amino acids, and the last 305 amino acids of the toxin) resulted in a relatively stable product in the supernatant of PAO-T1 . The product of the carboxy terminus construct (which codes for the last 305 amino acids of the toxin) was detected in the lysate of PAO-T1 only . The data suggest that the amino terminus region of toxin A (the leader peptide plus the first 30 amino acid of the mature protein) is sufficient for its excretion, and that a second region, amino acids 309 through 413, protects an internally truncated toxin A molecule from the proteolytic activity in the supernatant of P . aeruginosa PAO-T1.

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