Pseudomonas aeruginosa

Kosm Biol Aviakosm Med, 1985 Jul-Aug, 19(4), 74 - 6
{Formation of volatile substances during destruction of polymers by Pseudomonas aeruginosa}; Novikova ND et al.; The effect of biodestruction of paint-and-varnish coatings on the formation and evolution of toxic substances was studied . It was found that the multiplication of Pseudomonas aeruginosa on epoxide resins (EP-255 ++ EP-525/AK-070) modified the evolution of gases: that of acetone and n-butanone increased and evolution of xylene and ethyl benzene isomers decreased.

Antibiot Med Biotekhnol, 1985 Jul, 30(7), 511 - 6
{Comparative evaluation of 2 methods--dilution in agar and diffusion in agar--in determining Pseudomonas aeruginosa sensitivity to antibiotics}; Gabrielian SA et al.; Sensitivity of 200 strains of Pseudomonas aeruginosa to 8 antibiotics was studied with 2 methods, agar dilution and agar diffusion . The data obtained with the two methods were in good agreement . The simple method of agar diffusion provided sufficiently precise results in determination of the Pseudomonas sensitivity to carbenicillin and polymyxin . With the use of the correction principle by the "mobile intermediate zone" it also provided sufficiently precise results in determination of the Pseudomonas sensitivity to gentamicin . The necessity of using the reference strain ATCC 27853 of P . aeruginosa in every experiment is stressed . The peculiarities of the data interpretation in determination of antibiotic sensitivity of Pseudomonas are discussed.

Zh Mikrobiol Epidemiol Immunobiol, 1985 Jul, (7), 19 - 22
{Effect of plasmids on the virulence of Pseudomonas aeruginosa strains in experiments on mice}; Ianenko AS et al.; A comparative study of virulence of P . aeruginosa strains PAO containing and not containing plasmids has been made . A number of plasmids which are present in strains PAO decrease their virulence for mice 3-7 times . The virulence-affecting plasmids considerably differ in their biological properties . Bacterial mutations rpm, selected as mutations stabilizing RP4 plasmid in PAO cells, have also been found to affect virulence of bacteria, decreasing its level several times . The introduction of plasmids into PAO cells carrying mutations rpm is not accompanied by decrease of virulence.

Zh Mikrobiol Epidemiol Immunobiol, 1985 Jul, (7), 14 - 8
{Isolation and study of the properties of a polyvalent corpuscular Pseudomonas aeruginosa vaccine . An evaluation of the biological properties of a polyvalent corpuscular Pseudomonas aeruginosa vaccine}; Ttitova TI et al.; P . aeruginosa killed polyvalent corpuscular vaccine, tested in a trial on 42 volunteer donors, is safe, low reactogenic and possesses pronounced immunogenicity, as the injection of the vaccine induced a rise in the titer of antibodies to P . aeruginosa up to 1:1280 in 95% of the immunized donors . To obtain specific antibodies in the blood plasma of the donors in an amount sufficient for the protective activity of the plasma becoming manifest, it is expedient to use the vaccination schedule providing for subcutaneous injections of 0.5, 0.5 and 1.0 ml at intervals of 7 days . Intense immunity thus induced in the donors lasts for 3-4 months . The hyperimmune plasma obtained from the donors has an antibody titer of at least 1:320 and shows a 90-100% protective effect in mice infected intraperitoneally with P . aeruginosa . The preliminary results of the clinical trial of anti-P . aeruginosa plasma have demonstrated its efficiency as a part of the complex treatment of patients with purulent septic complications of P . aeruginosa etiology.

Rev Infect Dis, 1985 Jul-Aug, 7 Suppl 3, S411 - 6
Activity of imipenem against Pseudomonas and Bacteroides species; Williams JD; The activity of imipenem against Pseudomonas aeruginosa and Bacteroides fragilis in vitro was studied . MICs of imipenem for P . aeruginosa are approximately 2 micrograms/m . Unlike most other beta-lactam antibiotics, imipenem does not show cross-resistance in the presence of intrinsic resistance . Imipenem is a strong inducer of Id beta-lactamase but is stable to hydrolysis by this enzyme . B . fragilis is more susceptible to imipenem than to other beta-lactam antibiotics . The activity of imipenem against B . fragilis is similar to that of metronidazole . The cephalosporinases of B . fragilis do not inactivate imipenem.

Infection, 1985 Jul-Aug, 13(4), 184 - 9
In vitro activity of ceftazidime in combination with other antibiotics; Simon C et al.; 189 bacterial strains were investigated for their in vitro sensitivity against ceftazidime (alone and in combination with another antibiotic) . Moreover, the possibility to prevent development of secondary bacterial resistance as observed in subcultures at subinhibitory antibiotic concentrations, was studied using specific antibiotic combinations . Of 115 staphylococcal strains (91 strains of Staphylococcus aureus, 24 strains of Staphylococcus epidermidis), 2% were sensitive, 82% were moderately sensitive and 16% were resistant to ceftazidime . On combining ceftazidime with vancomycin, synergism was found in 61% of the strains, and secondary resistance to ceftazidime could be prevented with this combination . The combination of ceftazidime and clindamycin showed synergism in 26% and an additive effect in 48% of the strains . Secondary resistance to ceftazidime did not develop with this combination in subcultures at subinhibitory concentrations in which loss of activity was only minimal with clindamycin alone . Rifampicin and fusidic acid were highly active against staphylococci . In combination with ceftazidime, only weak synergism or additive effects were seen in most strains; no antagonism could be observed . In subcultures at subinhibitory concentrations, secondary resistance to rifampicin and fusidic acid developed rapidly and could be partially prevented by adding ceftazidime . Of 60 Pseudomonas aeruginosa strains, 84% were sensitive, 13% were moderately sensitive and 2% were resistant to ceftazidime . Synergism was most frequently observed when ceftazidime was combined with tobramycin . Using this combination, secondary resistance of Pseudomonas strains to ceftazidime did not develop . When ceftazidime was combined with piperacillin, synergism was observed in most strains, but the development of secondary resistance in vitro was not prevented.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrob Agents Chemother, 1985 Jul, 28(1), 64 - 8
Impact of netilmicin regimens on the activities of ceftazidime-netilmicin combinations against Pseudomonas aeruginosa in an in vitro pharmacokinetic model; Blaser J et al.; The antibacterial activities of ceftazidime and netilmicin were studied in a two-compartment in vitro model . Pseudomonas aeruginosa cultures were exposed to changing drug concentrations that mimic human pharmacokinetics . Netilmicin alone reduced the numbers of organisms in cultures of the susceptible strains by more than 99% within 4 h; however, regrowth occurred after 8 h . Although ceftazidime alone killed more slowly than netilmicin, only one of the five strains regrew within 28 h . When both drugs were combined, rapid initial killing occurred without subsequent regrowth . Studied after 24 h in combination with ceftazidime, netilmicin was as effective when given as a single daily dose as when administered in three daily doses that provided 50% more aminoglycoside per day . Decreased bacterial susceptibility was seen after ceftazidime exposure for one strain and after netilmicin exposure for all originally netilmicin-susceptible strains . No such reduction in susceptibility was observed during exposure to the combination . The results of standard in vitro checkerboard tests for synergism were predictive of the initial (4 to 8 h) but not the final (24 to 28 h) assessment of drug interaction in the pharmacokinetic model.

Antimicrob Agents Chemother, 1985 Jul, 28(1), 58 - 63
In vitro activity of BMY-28142 against pediatric pathogens, including isolates from cystic fibrosis sputum; Conrad DA et al.; The antibacterial activity of BMY-28142, a new aminothiazole cephalosporin, was measured by standardized broth microdilution and agar dilution methods against 450 gram-positive and gram-negative bacteria isolated from pediatric infections, including acute pulmonary exacerbations of cystic fibrosis . BMY-28142 activity was compared with that of aminoglycosides, beta-lactams, chloramphenicol, trimethoprim-sulfamethoxazole, vancomycin, and clindamycin . The activity of BMY-28142 in combination with other antimicrobial agents against Pseudomonas aeruginosa was also determined . Furthermore, the effects of inoculum and pH on BMY-28142 activity were evaluated . BMY-21842 was active against most of the gram-positive and gram-negative isolates, with the exception of methicillin-resistant Staphylococcus aureus and Pseudomonas cepacia . The combination of BMY-28142 with tobramycin was often synergistic, and combinations of BMY-28142 with either polymyxin B or imipenem were usually antagonistic . BMY-28142 antibacterial activity could be adversely affected at extremes of medium pH and by high inoculum densities.

Antimicrob Agents Chemother, 1985 Jul, 28(1), 41 - 5
Imipenem-induced resistance to antipseudomonal beta-lactams in Pseudomonas aeruginosa; Tausk F et al.; Using clinical isolates of Pseudomonas aeruginosa, we studied the ability of imipenem to antagonize the activity of nine other antipseudomonal beta-lactam antimicrobial agents . Imipenem caused truncation of the zones of inhibition in a disk diffusion test for 91 to 100% of the strains, depending on the beta-lactam tested . Addition of subinhibitory concentrations of imipenem caused a fourfold or greater increase in MICs for 72 of 74 isolates and in 20 to 87% of the tests, again depending on the antibiotic tested . beta-Lactamase assays with both whole-cell suspensions and cell sonicates showed that exposure to subinhibitory concentrations of imipenem resulted in a beta-lactamase production supported the hypothesis that induction of beta-lactamase was responsible for antagonism . In hydrolysis studies with a beta-lactamase extract, most of the antagonized drugs were either not hydrolyzed or only poorly hydrolyzed . We conclude that imipenem induces significantly elevated levels of beta-lactamase in P . aeruginosa . This increase in beta-lactamase is associated with increased resistance of the organism to many other beta-lactam agents.

Antimicrob Agents Chemother, 1985 Jul, 28(1), 160 - 2
Comparative in vitro inhibitory and killing activity of cefpirome, ceftazidime, and cefotaxime against Pseudomonas aeruginosa, enterococci, Staphylococcus epidermidis, and methicillin-susceptible and -resistant and tolerant and nontolerant Staphylococcus aureus; Goldstein EJ et al.; With a macrotube dilution method, MICs and MBCs were determined for three aminothiazolyl cephalosporins, cefpirome (HR 810), ceftazidime, and cefotaxime, against Pseudomonas aeruginosa, enterococci, Staphylococcus epidermidis, and methicillin-resistant, -susceptible, and -tolerant strains of Staphylococcus aureus . Comparatively, cefpirome was the most active agent against all gram-positive cocci, including enterococci and methicillin-resistant S . aureus, and was as active as ceftazidime against P . aeruginosa . MBCs of cefpirome were within two dilutions of the MICs for 91% of P . aeruginosa and 90% of gram-positive cocci strains tested, except methicillin-resistant S . aureus, for which the MBCs were within three dilutions for 90% of strains.

J Biol Stand, 1985 Jul, 13(3), 235 - 42
The influence of immunoglobulin on the development of Pseudomonas aeruginosa infection in an immunocompromised mouse model; Jupa-Marcinkowski V et al.; Pretreatment with normal immunoglobulin G (normal IgG) isolated from human placental blood, in secondary immune deficiency after anaesthesia, surgery and corticosteroid therapy seems to be an effective protection against bacterial infection in clinical practice . For this purpose, we tried to verify the effectiveness of normal IgG in prevention of bacterial infection in an animal model . The influence of treatment with normal human IgG has been studied in mice exposed to a sublethal infection with Pseudomonas aeruginosa in various states of immunocompetence such as under anaesthesia and corticosteroid therapy . Results, evaluated as percentages of survivors, confirm significant protection against infection with P . aeruginosa despite immunodepression with hydrocortisone and anaesthesia (96.6% of survivors in the group treated with IgG as opposed to 30% for the untreated corresponding group--P less than 0.001).

Biull Eksp Biol Med, 1985 Jul, 100(7), 57 - 60
{Structural bases for the invasion of the causative agents of experimental Pseudomonas aeruginosa sepsis into the bloodstream from the primary septic focus}; Panova NV et al.; The soft tissues around the implant with a suspension of P . aeruginosa were studied by light and electron microscopy . Severe damages to structures of the histohematic barrier, phagocytes were revealed as was the bacterial invasion into thrombosed vessels of the microcirculatory bed . The mechanism of the micrometabolism as playing the key role in the bacterial penetration from the primary septic focus into the common bloodstream is discussed.

Arch Dermatol, 1985 Jul, 121(7), 873 - 6
Pseudomonas aeruginosa O-11 folliculitis . Development into ecthyma gangrenosum in immunosuppressed patients; El Baze P et al.; Six immunocompromised patients were shown to exhibit Pseudomonas aeruginosa folliculitis in apocrine regions similar to "swimming pool" folliculitis . The lesions evolved within 24 hours as severe ecthyma gangrenosum . The source of the P aeruginosa, serotype O-11, was found in the water system of the hospital . Clinical identification of the lesions and early treatment is important to prevent severe manifestations.

Infect Immun, 1985 Jul, 49(1), 182 - 9
Role of lipopolysaccharide in opsonization and phagocytosis of Pseudomonas aeruginosa; Engels W et al.; When the opsonization of various Pseudomonas aeruginosa strains--PAC 1, its O-chain-deficient mutant PAC 605, and an intermediate strain, P14--was measured either directly by determination of the amount of C3b attached to the bacterial surface or indirectly by assessing phagocytosis by human polymorphonuclear leukocytes and the responses of chemiluminescence, it was demonstrated that PAC 1 was opsonized and phagocytized to a lower extent than P14 and PAC 605 . In contrast to PAC 605, PAC 1 showed an increased consumption of complement in the fluid phase and a rapid release of lipopolysaccharide antibodies bound to the bacterial surface due to the alternative pathway of the complement system . Furthermore, it was shown that with respect to PAC 1 and PAC 605, the lack of an O-chain resulted in increased sensitivity to serum and decreased virulence . From both in vivo and in vitro experiments, we concluded that the structure of the O-antigen polysaccharide chain of lipopolysaccharide is an important virulence factor of P . aeruginosa against the defense mechanisms of the host.

Rev Infect Dis, 1985 Jul-Aug, 7 Suppl 3, S482 - 9
Imipenem/cilastatin in acute pulmonary exacerbations of cystic fibrosis; Krilov LR et al.; Nineteen patients with pulmonary exacerbations of cystic fibrosis due to Pseudomonas aeruginosa were given imipenem/cilastatin for six to 10 days at dosages of 30-90 mg/kg per day . Mean Shwachman scores rose from 46.6 to 50.3 (P less than .001), clinical efficacy scores from 34.3 to 43.3 (P less than .001), vital capacity from 53.7% to 58.5% of the predicted value (P less than .01), forced expiratory volume in 1 sec from 39.5% to 42.6%, and partial pressure of oxygen in arterial blood from 68.2 mm Hg to 72.6 mm Hg . Treatment failed in only two instances . The concentration of P . aeruginosa in the sputum decreased to a modest extent (8.5 log10 cfu/ml on day 1, 8.1 log10 cfu/ml on day 10; P greater than .1) . Four patients had imipenem-resistant strains of P . aeruginosa at the start of therapy, and 11 additional patients developed resistant strains during treatment; in eight patients greater than 90% of all Pseudomonas organisms in the sputum were resistant at the end of therapy . Six patients acquired Candida in their sputum . There was no correlation between bacteriologic improvement or the development of resistance to imipenem and either clinical outcome or improvement in pulmonary function . In summary, imipenem/cilastatin therapy is associated with a good clinical outcome in patients with cystic fibrosis, but resistance emerges rapidly.

Ann Rheum Dis, 1985 Jul, 44(7), 499 - 500
Pseudomonas arthritis treated with parenteral and intra-articular ceftazidime; Walton K et al.; A 73-year-old diabetic presented with septic arthritis of the knee; Pseudomonas aeruginosa was isolated . She was successfully treated with a combination of parenteral and intra-articular ceftazidime, after failure to eradicate the organism with adequate serum levels of gentamicin and full doses of azlocillin.

Infect Immun, 1985 Jul, 49(1), 132 - 40
Effects of siderophores on the growth of Pseudomonas aeruginosa in human serum and transferrin; Ankenbauer R et al.; A combination of the siderophores produced by Pseudomonas aeruginosa, pyochelin and pyoverdin, dramatically stimulates the growth of this bacterium in medium containing human transferrin . The amount of growth stimulation observed when each siderophore was added alone was only slightly less than the amount observed with the combination . Siderophore-defective mutants of strain PAO1 were isolated to test the effects of siderophore production on growth in transferrin and human serum . The pyoverdin-proficient (Pvd+), pyochelin-deficient (Pch-) strain (IA5) grows just as well as the parent (PAO1), which produces both siderophores . On the other hand, the Pvd- Pch+ strain (211-5) has severely retarded growth, similar to that demonstrated by a mutant lacking production of both siderophores (IA1), but has an accelerated log phase compared with strain IA1 at the later stages of the growth curve . However, the Pvd- Pch+ strain (211-5) had no observable advantage over the Pvd- Pch- strain, IA1, during incubation in human serum . The inability of P . aeruginosa strains to produce pyochelin in glucose-minimal medium may explain the poor growth of 211-5 in this medium and in human serum . The 211-5 strain grows much better than the IA1 strain in the medium that allows pyochelin synthesis, but it still does not grow as well as the Pvd+ Pch- strain (IA5) . Therefore, pyoverdin appears to be the most important siderophore for growth in human serum.

Antibiot Med Biotekhnol, 1985 Jul, 30(7), 503 - 7
{Genetic and physicochemical analysis of the resistance of Pseudomonas aeruginosa strains to gentamycin and other antibiotics}; Vakulenko SB et al.; The genetic and physicochemical mechanisms of antibiotic resistance were studied in 50 clinical strains of P . aeruginosa resistant to gentamicin . The serotypes and pyocinotypes of the bacteria were determined . The spectra and levels of antibiotic resistance and the plasmid profiles of the strains were estimated . It was shown that 16 multiresistant isolates had identical spectra and levels of antibiotic resistance, belonged to the same serotype and pyocinotype and were characterized by the absence of the extrachromosomal DNA, which indicated the circulation of the same polyresistant strain in hospital . Plasmids with identical molecular weights and antibiotic resistance spectra were detected in 14 strains belonging to different serotypes and pyocinotypes . These plasmids determined synthesis of the same aminoglycoside inactivating enzymes: APH (3') and AAC (3) . Epidemiologic distribution of the same high molecular R plasmid among the clinical strains of P . aeruginosa is suggested.

Infection, 1985 Jul-Aug, 13(4), 177 - 8
Ciprofloxacin-induced hematuria; Garlando F et al.; We used ciprofloxacin, a quinolone-derivative, to treat a lung infection due to Pseudomonas aeruginosa in an adult cystic fibrosis patient . On three different occasions the use of ciprofloxacin was associated with the development of an asymptomatic hematuria with red blood cell casts . The mechanism responsible for this hematuria is presently unknown, but clinicians should be aware of this potential adverse effect of ciprofloxacin.

Am J Med, 1985 Jun 28, 78(6B), 17 - 22
Antimicrobial activity, bacterial resistance, and antimicrobial pharmacology . Is it possible to use new agents cost-effectively?
Neu HC.
Perusal of the various journals devoted to antimicrobial agents and to the chemotherapy of infectious diseases reveals an increasing number of articles devoted to the analysis of the pharmacology of antimicrobial agents and the relationships of antimicrobial activity and pharmacologic properties . However, most attention to the pharmacokinetic properties of antimicrobial agents in the past decade has focused on the toxic properties of these agents, and there has been little work devoted to improving methods of administration . The availability of nontoxic antibiotics that are extremely active at low concentrations and of agents with markedly extended half-lives should cause us to reevaluate some of our current dosing practices . In many ways, a major adverse influence on appropriate antimicrobial therapy of ordinary infections has been the febrile neutropenic patient . Lessons learned from the care of these patients are inappropriately applied to the treatment of other patients . The neutropenic patient requires frequent administration of antibiotics at maximally tolerated doses . Many patients at risk for infection do not require antimicrobial therapeutic programs in which the antibiotic always exceeds the minimal inhibitory concentration . Indeed, the concept that the drug must be present in the serum well above the minimal inhibitory concentration for the entire interval of infection is derived from studies of neutropenic patients infected with Pseudomonas aeruginosa . Increasing resistance of hospital-acquired bacteria to older antibacterial agents will alter the initial and subsequent selection of antimicrobial agent . Combination drug therapy, which has a prominent role in the neutropenic patient, frequently results in greater cost to the health care system than is seen with single agents that are active against resistant bacteria . There are clear areas in which new antibacterial agents will be beneficial . We may be at a stage in which use of the older agents can no longer be viewed as the best clinically and economically . Better use of twice- or once-daily dosing programs of new agents coupled with use of intramuscular and oral administration of antibiotics can help reduce nosocomial infections that contribute to rising health costs.

Pharm Weekbl Sci, 1985 Jun 21, 7(3), 100 - 3
The bactericidal activity of aqueous disinfectants applied on living tissues; Reybrouck G; Thirteen antiseptic aqueous solutions intended for the disinfection of living tissues were compared in regard to their microbicidal effectiveness towards . Staphylococcus aureus and Pseudomonas aeruginosa . Six antiseptics, which contain boric acid, eosine, hydrogen peroxide or an organic mercury compound as the active substance, did not fulfil the requirements of the preliminary in vitro test . The seven other preparations were examined in a practical test, in which bactericidal activity was assessed on artificially contaminated intact skin after exposures of 15 s and 60 s . The most active solution appeared to be 0.5% tosylchloramide sodium, followed by 0.05% chlorhexidine with 0.5% cetrimide . The other preparations, namely 0.05% chlorhexidine without cetrimide, 0.245% chloroxylenol, 0.04% clorofene, 10% povidone-iodine and 0.2% tosylchloramide sodium, were less active in this practical test.

Klin Wochenschr, 1985 Jun 3, 63(11), 490 - 8
{Infections of the respiratory tract with Pseudomonas aeruginosa in cystic fibrosis}; Winkler U et al.; The main cause of death in cystic fibrosis (CF) patients is progressive pulmonary insufficiency frequently associated with chronic infections of the respiratory tract by Pseudomonas aeruginosa . Bacteria of this species synthesize numerous extracellular products contributing to its pathogenicity . An alginate-like exopolysaccharide is characteristic for mucoid mutants predominating among P . aeruginosa isolates from CF patients . It interferes with immune defense mechanisms of the host and probably protects the bacteria against certain antibiotics . Furthermore, it is involved in the formation of bacterial microcolonies that resist mucociliary clearance, opsonisation, and phagocytosis . Exotoxin A and elastase are regarded as the most important among various extracellular enzymes involved in pulmonary injury in CF patients . Exotoxin A inhibits eukaryotic protein synthesis leading to necrosis; elastase, together with other Pseudomonas-proteases, induces hemorrhagic lesions and necrosis and seems to inactivate immunoglobulins and complement factors . Phospholipase C and glycolipid represent two hemolysins of P . aeruginosa that may contribute to cytopathogenic effects in infected lungs . No primary defect in the immunological defense mechanisms of CF patients has been described so far . Antibodies against various P . aeruginosa antigens including those mentioned above have been demonstrated, but a complete elimination of the bacteria from infected lungs has not been observed . Therapy of pulmonary P . aeruginosa infections in CF patients usually includes combinations of antibiotics of the beta-lactam and aminoglycoside type . Difficulties arise from an unusually high intrinsic resistance of P . aeruginosa as well as from poor penetration of many antibiotics into the sputum of CF patients . Therefore, future efforts to manage the Pseudomonas problem in CF will probably concentrate on prophylactic therapy, e.g . childhood vaccination of CF patients in order to prevent bacterial colonization of the respiratory tract.

J Clin Lab Immunol, 1985 Jun, 17(2), 85 - 9
The in vitro effect of three antibiotics on alveolar macrophages; Oliver AM et al.; The effects of 3 antibiotics, azlocillin, ticarcillin and tobramycin, on rat alveolar macrophage function has been examined . These antibiotics are used in the treatment of Pseudomonas aeruginosa lung infections in cystic fibrosis patients . In this study low concentrations of the antibiotics were used, similar to the low levels found in the lungs of these patients . Tobramycin, a highly active aminoglycoside, inhibited the phagocytosis of opsonized Pseudomonas aeruginosa and enhanced the binding of sheep erythrocytes sensitized with IgG2b, when pre-incubated with macrophage monolayers for 30 min . Inhibition of both phagocytosis and binding of sensitized sheep erythrocytes was observed when tobramycin was co-incubated with the macrophage monolayers and indicator cells . Azlocillin, a semi-synthetic penicillin, caused inhibition of phagocytosis of opsonized bacteria and binding of sensitized sheep erythrocytes when added with the indicator cells . However, no effect was found if the macrophages were pre-incubated with azlocillin for 30 min . Ticarcillin, a semi-synthetic penicillin which is less active in vitro as an antimicrobial agent than azlocillin, had no effect on alveolar macrophages at the concentrations used in these assays . It is postulated that if these in vitro findings with rat alveolar macrophages are reflected in the in vivo situation in humans, the effect of antibiotics on host defence may be of clinical importance.

Burns Incl Therm Inj, 1985 Jun, 11(5), 337 - 42
Bacteriological effect of cerium-flamazine cream in major burns; Boeckx W et al.; A controlled trial of the use of either 0.05 per cent chlorhexidine for bathing burn wounds or the topical application of a cream containing cerium nitrate and silver sulphadiazine showed that the cerium-flamazine cream significantly reduced the degree of Pseudomonas aeruginosa contamination of the burn wounds of patients with burns covering more than 15 per cent of the body surface area . The adherent eschar produced by treatment with cerium-flamazine provided a satisfactory wound cover until tangential excision could be carried out.

J Antibiot (Tokyo), 1985 Jun, 38(6), 740 - 5
Synthesis and antimicrobial activity of pyrimidinylureidocephalosporins; Wetzel B et al.; The synthesis of a series of 7R-{(R)-2-{3-{5-pyrimidinyl}ureido}-2-(aryl)acetamido}-3-cephem-4- carboxylates is described . Variation of the substituents at the 3-position in the cephem nucleus, at the 2-position of the pyrimidine ring, and of the phenyl residue in the acyl side chain is carried out . Qualitative structure-activity relationships in this series are discussed . VX-VD 2, the most interesting compound, exhibits broad antimicrobial activity against Gram-negative bacteria, including Pseudomonas aeruginosa.

Arch Intern Med, 1985 Jun, 145(6), 1073 - 8
Long-term intravenous antibiotic therapy in chronic osteomyelitis; Wagner DK et al.; Because the optimal treatment of chronic osteomyelitis is not well established, we studied the efficacy of prolonged (three months or more) outpatient intravenous antibiotic therapy via a Hickman catheter . Seventeen patients were entered into our protocol (13 with chronic osteomyelitis, three with chronic septic arthritis, and one with subacute osteomyelitis) . Pseudomonas aeruginosa was the most common bone isolate, followed by Staphylococcus aureus . Most patients had polymicrobial isolates . Patients were followed up with clinical examinations, serial measurements of erythrocyte sedimentation rate, and scans using technetium Tc 99m medronate and gallium citrate Ga 67 . Of the ten patients with chronic osteomyelitis who completed therapy, eight were considered cured . After further follow-up, three of the cured patients had recurrences requiring additional therapy.

Am Rev Respir Dis, 1985 Jun, 131(6), 845 - 9
Intrapulmonary chemotaxins in the normal and in the cyclophosphamide-treated host; Pennington JE et al.; The kinetics of intrapulmonary chemotactic activity and the generation of a pulmonary polymorphonuclear leukocytic (PMN) response during experimental Pseudomonas aeruginosa pneumonia were studied in normal and in cyclophosphamide-treated guinea pigs . In normal animals, chemotactic activity for PMN appeared in airways promptly (2 h) after infection and preceded the influx of PMN to infected airways . Week-long regimens of intraperitoneally administered cyclophosphamide, in dosages of 7.5 mg/kg/day (low-dose) or 15 mg/kg/day (high-dose), resulted in systemic myelosuppression accompanied by a dose-related decrease in recruitment of PMN to infected airways . The chemotactic activity assayed in bronchoalveolar fluids obtained from low-dose-treated animals was not affected by cyclophosphamide . However, chemotactic activity in bronchoalveolar fluids was significantly reduced (p less than 0.01) in animals receiving the high-dose cyclophosphamide regimen . Gel chromatography of bronchoalveolar fluids from infected animals revealed that a high molecular weight (20,000 daltons or greater) and a low molecular weight (5,000 daltons) chemotactic factor were present in normal specimens, and that both were absent from specimens obtained from animals receiving the high-dose treatment . Hemolytically active C5 was detected in infected bronchial fluids, but cyclophosphamide treatment did not reduce amounts of C5 in infected airways . These data suggest that in addition to myelosuppression, cyclophosphamide treatment impairs the capacity for pulmonary inflammation by reducing the normal intrapulmonary chemotactic gradient during infection.

Eur J Epidemiol, 1985 Jun, 1(2), 104 - 9
Infections caused by Pseudomonas aeruginosa: relatively frequent isolation of serogroup 12 from clinical specimens; Giammanco A et al.; Serological typing of P . aeruginosa is the most simple and reliable procedure recommended for "in-house" investigations and for studies of suspected outbreaks of infection by this microorganism . It is also a useful procedure in order to know serotype prevalence in a definite geographical area and to obtain indications about the more appropriate composition of polyvalent anti-Pseudomonas vaccines . In the present report, we describe the relatively high frequency of isolation of serogroup 12 from patients in Palermo, Italy . Serogroup 12 is very rare in north-Europe and in the USA, and, as a consequence, it is not included in some vaccine preparations . In Palermo, strains belonging to this serogroup, resistant to a large number of antibiotics, were on the contrary isolated, during more than six years, in different hospitals and from three out-patients . In a Burns Unit, they were in particular responsible for extensive and life-threatening outbreaks.

Jpn J Antibiot, 1985 Jun, 38(6), 1529 - 32
{In vitro study on the combined effect of mezlocillin and sisomicin on clinically pathogenic P . aeruginosa and E . coli}; Shishido H et al.; Clinically pathogenic Pseudomonas aeruginosa and Escherichia coli were subjected to test in vitro combination effect of mezlocillin (MZPC) and sisomicin (SISO) . The chequer board titration method, using brain heart infusion broth (BHIB, Difco), demonstrated the combination effect of MZPC and SISO on the both isolates . The bactericidal combination effects (MBCs) were clearly higher than the bacteriostatic combination effects (MICs) . The bactericidal activities of combination with MZPC and SISO were tested on both P . aeruginosa and E . coli . The MZPC plus SISO of low concentrations showed the synergistic effects on both isolates.

Acta Pathol Microbiol Immunol Scand {B}, 1985 Jun, 93(3), 217 - 23
Exotoxin A from various Pseudomonas aeruginosa cultures: in vitro activity measured by enzyme-linked immunosorbent assay (ELISA); Ogaard AR et al.; An enzyme-linked immunosorbent assay (ELISA) for the detection of Pseudomonas aeruginosa exotoxin A (toxin A) was developed . The level of toxin A produced by fresh P . aeruginosa isolates was compared to the level of toxin A produced by twelve-months-old subcultures derived from the same strains . Results obtained with the ELISA showed that toxin A was produced in similar amounts both by the fresh isolates and the subcultures . The production of toxin A seems to represent a stable property of the assayed P . aeruginosa strains . This is in contrast to other exoproducts from the same strains, such as extracellular proteinases . Some proteinases were produced at very different levels when freshly isolated P . aeruginosa cultures were compared with their twelve-months-old counterparts, confirming earlier reports in this respect.

Acta Pathol Microbiol Immunol Scand {B}, 1985 Jun, 93(3), 211 - 6
Correlation between adhesion of Pseudomonas aeruginosa bacteria to cell surfaces and the presence of some factors related to virulence; Ogaard AR et al.; Recent isolates of Pseudomonas aeruginosa strains and 12-month-old subcultivated variants of the same strains have been assayed for adhesiveness to HEp-2 cells . P . aeruginosa adhesion factors were located both to the bacterial surface and extracellularly . Generally, loss of adhesiveness upon subcultivation could be restituted by adding extracellular factor from the recent isolate . While the extracellular adhesins were neutralized by non-specific serum factors, the surface-bound adhesins of a recent isolate were blocked by antibodies only.

Vaccine, 1985 Jun, 3(2), 128 - 36
Vaccines against Pseudomonas aeruginosa infection: 1 . Experimental studies; Stanislavsky ES et al.; An experimental study of several types of vaccines against Pseudomonas aeruginosa has been carried out . Pyoimmunogen, a multi-component vaccine consisting mainly of heat-stable proteins (or polypeptides) with a molecular weight of 20 000 to 60 000, was prepared both by laboratory and production techniques using three or five selected strains of P . aeruginosa . The preparations obtained by both methods were found to be of low toxicity and to induce in mice and rats active immunity against challenge with homologous and some heterologous strains of P . aeruginosa, including the toxigenic PA-103 strain . The Pseudomonas vaccine (PV) was prepared from partly purified water-soluble protein antigens (molecular weight ranging from 10 000 to 100 000) obtained from one (mono-PV) or three (tri-PV) selected strains . Mono-PV was prepared by the method of ultrafiltration and tri-PV--by differential centrifugtion . Both types of vaccines proved effective in active mouse protection tests after challenge with homologous as well as with heterologous P . aeruginosa strains . Mono-PV is supposed to induce species-specific immunity against P . aeruginosa infection in mice.

J Antimicrob Chemother, 1985 Jun, 15(6), 665 - 70
Mutation of Pseudomonas aeruginosa to piperacillin resistance mediated by beta-lactamase production; Bell SM et al.; Piperacillin-resistant mutants were detected in each of ten strains of Pseudomonas aeruginosa . The resistance was associated with constitutive production by the strains of high levels of beta-lactamase which was similar in character to the induced chromosomal Id beta-lactamase of the parent strains . This type of mutation to piperacillin-resistance occurred at a low frequency . The beta-lactamase production and piperacillin-resistance were stable on repeated subculture and prolonged storage of the strains.

Oral Surg Oral Med Oral Pathol, 1985 Jun, 59(6), 590 - 4
Pseudomonas aeruginosa in the oral cavity and sputum of patients with cystic fibrosis; Komiyama K et al.; Patients with cystic fibrosis (CF) are often hosts to colonies of both mucoid and nonmucoid strains of Pseudomonas aeruginosa . The major pathogens for chronic and recurrent pulmonary infection in these patients are the mucoid variants of P . aeruginosa . Of the 31 CF patients studied, 14 patients yielded both mucoid and nonmucoid strains of P . aeruginosa from the various oral ecologic sites and saliva . Of the sites tested, the dorsum of the tongue gave the highest yield of P . aeruginosa (27 strains), followed by the buccal mucosa (17 strains), saliva (15 strains), and dental plaques (6 strains) . Eleven patients had P . aeruginosa in the oral cavity and sputum simultaneously . Antibiotic susceptibility tests on these multiple isolates suggest that CF patients may be cocolonized or coinfected by two or more strains of P . aeruginosa . Therefore, it may be important to identify multiple isolates of P . aeruginosa, not only from sputum cultures but also from oral cultures, for antibiotic-susceptibility testing . Oral colonization by the mucoid variants of P . aeruginosa may lead to further colonization in the lower respiratory tract and subsequent pulmonary infection in CF patients.

J Bacteriol, 1985 Jun, 162(3), 872 - 80
Chromosomal mapping of mutations affecting glycerol and glucose catabolism in Pseudomonas aeruginosa PAO; Cuskey SM et al.; Mutations causing deficiencies in the inducible, membrane-associated sn-glycerol-3-phosphate dehydrogenase (glpD) and in inducible glucose transport (glcT) were mapped on the Pseudomonas aeruginosa PAO1 chromosome by using the generalized transducing phages F116L and G101 . These mutations, in separate catabolic regulatory units, were cotransducible with a previously described cluster of carbohydrate catabolic gene loci (zwf-1 eda-9001 edd-1) that maps at ca . 50 to 53 min on the chromosome . Mutant strain PFB362 (glcT1) did not transport glucose and did not produce a functional, periplasmic, glucose-binding protein that is required for glucose transport . This mutation was cotransducible with zwf-1 (70%), nalA (29%), and phe-2 (19%) but not with glpD1 or leu-10 . The glpD1 mutation in strain PRP408 was cotransducible with zwf-1 (5%), eda-9001 (4%), and edd-1 (1%) and also with ami-151 (17%) and phe-2 (33%) . These results expand the number of known carbohydrate catabolism genes that are clustered in the 50- to 55-min region of the PAO1 chromosome and allow us to propose the following relative gene order: ami-151 glpD1 phe-2 nalA zwf-1 eda-9001 edd-1 glcT1 leu-10 . Three independently obtained nal determinants for high-level resistance to nalidixic acid, which were employed in these studies, exhibited similar cotransduction frequencies with several flanking marker mutations.

J Bacteriol, 1985 Jun, 162(3), 1329 - 31
Genetic mapping and characterization of Pseudomonas aeruginosa mutants that hyperproduce exoproteins; Bjorklind A et al.; We isolated two mutants of Pseudomonas aeruginosa PAO with defective iron uptake . In contrast to the wild-type strain, the mutants produced extracellular protease activity in media containing high concentrations of salts or iron and hyperproduced elastase, staphylolytic enzyme, and exotoxin A in ordinary media (Xch mutants) . The mutations were located in the 55' region of the chromosome, between the markers met-9011 and pyrD.

Infect Immun, 1985 Jun, 48(3), 648 - 51
Effect of calcium chloride on experimental infection of mice with Pseudomonas aeruginosa; Tamura Y et al.; Concomitant administration of Pseudomonas aeruginosa and calcium chloride to mice enhanced the virulence of some strains . The 50% lethal dose of P . aeruginosa 5 decreased by more than three orders of magnitude, regardless of the challenge route (intramuscular, subcutaneous, and intraperitoneal injection), while the 50% lethal dose of strain N10 did not decrease . When challenged intramuscularly with 10(4) organisms of strain 5 or strain N10 mixed with calcium chloride, both strains multiplied at the local site of injection . Strain 5 subsequently caused systemic infection, while strain N10 did not . The virulence-enhancing effect of calcium chloride can be successfully applied in protection assays for immunized mice challenged with strain 5.

J Immunol, 1985 Jun, 134(6), 4112 - 7
In vitro T cell-mediated killing of Pseudomonas aeruginosa . II . The role of macrophages and T cell subsets in T cell killing; Markham RB et al.; T lymphocytes from immune mice can adoptively transfer protection against infection with the extra-cellular Gram-negative bacterium Pseudomonas aeruginosa to nonimmune recipients, and in vitro, immune T cells are able to kill these bacteria . Earlier studies indicated that this killing is mediated by a bactericidal lymphokine . Those studies also showed that macrophages enhance this in vitro T cell killing but do not directly participate in the bacterial killing, nor do macrophages function to present antigen to T cells . The current studies demonstrate that the ability of macrophages to enhance T cell killing can be replaced by macrophage culture supernatants or by purified recombinant interleukin 1 (IL 1) . In addition, the macrophage supernatant-induced enhancement can also be blocked by antibody to purified IL 1 . These studies also demonstrate that the T cell subset that serves as the final effector cell in the killing process is the Lyt-1-, 2,3+, I-J+ phenotype.

J Antimicrob Chemother, 1985 Jun, 15(6), 679 - 84
In-vitro activity of ciprofloxacin and other antibacterial agents against Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients; Klinger JD et al.; The in-vitro activities of ciprofloxacin, a new oxyquinoline derivative, norfloxacin and six anti-pseudomal beta-lactam antibiotics were tested against pulmonary isolates of smooth and mucoid colony forms of Pseudomonas aeruginosa, and Ps . cepacia from children with cystic fibrosis . Ciprofloxacin was the most effective of the agents tested against either species . Minimal inhibitory concentrations of ciprofloxacin were 0.5, and 16 mg/l, for 90% of the Ps . aeruginosa and Ps . cepacia strains tested, respectively . No effect of inoculum size or discordance between inhibitory or bactericidal concentrations was observed . Ciprofloxacin is a potentially useful agent for the treatment of acute pseudomonal pulmonary exacerbations in children with cystic fibrosis.

Biochem Soc Trans, 1985 Jun, 13(3), 619 - 22
Electron-paramagnetic-resonance studies of structure and function of the two-haem enzymes Pseudomonas cytochrome c peroxidase and beef heart cytochrome c oxidase; Vanngard T; Beef heart cytochrome c oxidase contains two cytochromes, a and a3, and Pseudomonas aeruginosa cytochrome c peroxidase has one high- and one low-potential c haem, cHP and cLP . The parallelism in co-ordination and spin states between cytochrome a and haem cHP on the one hand and between cytochrome a3 and haem cLP on the other is illustrated . The two latter haems become accessible to cyanide, when the former are reduced . Such reduction also leads to an activation of the enzymes . Mechanisms are presented in which ferryl forms of cytochromes a3 and haem cLP take part . The enzymes reach an oxidation state, formally the same as resting enzyme, but with different properties.

J Med Microbiol, 1985 Jun, 19(3), 375 - 81
Outer surface changes of Pseudomonas aeruginosa in relation to resistance to gentamicin and carbenicillin; Katsorchis T et al.; The outer surface structure of clinical isolates of Pseudomonas aeruginosa resistant to carbenicillin or gentamicin or both was studied by thin-section electronmicroscopy and compared with that of sensitive isolates . The latter had a fairly smooth outer layer . Strains resistant to both antibiotics were characterised by extrusions that appeared to constitute extensions of the outer membrane . The outer membrane appeared wavy with distortion of its tripartite structure . The latter findings were also present in isolates resistant to only one of the two antibiotics . The disorganisation of the outer membrane might contribute to the expression of resistance.

J Bacteriol, 1985 Jun, 162(3), 1068 - 74
Method for gene replacement in Pseudomonas aeruginosa used in construction of recA mutants: recA-independent instability of alginate production; Ohman DE et al.; The availability of a technique for site-directed mutagenesis by gene replacement provides a powerful tool for genetic analysis in any bacterial species . We report here a general technique for gene replacement in Pseudomonas aeruginosa . Genes on fragments of cloned P . aeruginosa DNA, altered by transposon mutagenesis, can be transduced into a recipient strain and can replace homologous genes in the P . aeruginosa genome . In this study we applied this technique to the construction of recA mutants of P . aeruginosa . A cloned segment of P . aeruginosa FRD1 DNA was isolated which encoded a protein analogous to the recA gene product of Escherichia coli . The P . aeruginosa recA gene was able to complement several defects associated with recA mutation in E . coli . Transposon Tn1 and Tn501 insertions in the cloned recA gene of P . aeruginosa were used to generate chromosomal recA mutants by gene replacement . These recA strains of P . aeruginosa were more sensitive to UV irradiation and methyl methane sulfonate and showed reduced recombination proficiency compared with the wild type . Also examined was the effect of recA mutations on the expression of alginate, a virulence trait . Alginate is a capsulelike polysaccharide associated with certain pulmonary infections, and its expression is typically unstable . The genetic mechanism responsible for the instability of alginate biosynthesis was shown to be recA independent.

Can J Microbiol, 1985 Jun, 31(6), 563 - 9
Adhesion of Pseudomonas aeruginosa to human buccal epithelial cells: evidence for two classes of receptors; McEachran DW et al.; The adhesion of Pseudomonas aeruginosa strain 492c to trypsinized and untrypsinized buccal epithelial cells (BECs) was studied . Kinetic analysis of the adhesion data, employing a Langmuir absorption isotherm, indicated the presence of two classes of binding sites on untrypsinized BECs: a high affinity - low copy number site (apparent association constant (Ka) approximately equal to 1.57 X 10(-8) mL/cell with ca . 29 binding sites/cell) and a low affinity - high copy number class of binding sites (Ka approximately equal to 4.78 X 10(-10) mL/cell with ca . 264 binding sites/cell) . The low affinity - high copy number class of sites was found to be trypsin sensitive . A single class of binding sites was found on trypsinized BECs exhibiting a high affinity - low copy number (Ka approximately equal to 3.70 X 10(-7) mL/cell with ca . 31 binding sites/cell) . Positive cooperativity in binding of P . aeruginosa strain 492c to the low affinity - high copy number class site on untrypsinized BECs was demonstrated by analysis of Hill plots of the adhesion data . Sugar inhibition data using a preincubation methodology showed an inhibition of adhesion to trypsinized BECs in the presence of N-acetylneuraminic acid and D-arabinose, while these same two sugars enhanced adhesion to untrypsinized BECs . D-Galactose and N-acetylglucosamine enhanced adhesion to both types of BECs though the latter did to different extents . D-Fucose only inhibited adhesion to untrypsinized BECs.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochim Biophys Acta, 1985 May 29, 840(1), 137 - 40
Prostaglandin E2 and muscle protein turnover in Pseudomonas aeruginosa sepsis; Turinsky J et al.; Rats were injected intraperitoneally with Pseudomonas aeruginosa (septic group) or sterile 0.9% NaCl (controls) . Soleus muscles were excised 7 h later, and muscle prostaglandin E2 release and tyrosine release were measured in vitro . Muscles of septic rats exhibited 226-326% higher release of prostaglandin E2 and 54-84% higher net proteolysis than muscles of controls . Inclusion of aspirin or indomethacin in the incubation medium almost completely inhibited prostaglandin E2 production, but had no effect on net proteolysis in muscles from either group . Inclusion of cycloheximide, a protein synthesis inhibitor, increased tyrosine release of control muscles by 42%, whereas no statistically significant increase was observed in muscles from infected rats . However, total proteolytic rate, indexed by tyrosine release in the presence of cycloheximide, was 22% higher in muscles of septic rats compared to that of control animals . Concomitantly, inclusion of cycloheximide inhibited prostaglandin E2 release by muscles of infected rats by 91% and that of controls by 65% . It is concluded that muscles of septic animals exhibit a pronounced stimulation of prostaglandin E2 release and net proteolysis, combined with a small increase in total proteolytic rate, the stimulation of net proteolysis is mainly due to inhibition of protein synthesis, the increases in net and total proteolysis appear to be independent of prostaglandin E2 production, cycloheximide has a previously unrecognized inhibitory effect on muscle prostaglandin E2 production.

Experientia, 1985 May 15, 41(5), 681 - 2
Pseudomonas lectin PA-I detects hybrid product of blood group AB genes in saliva; Gilboa-Garber N et al.; Pseudomonas aeruginosa galactophilic lectin PA-I exhibits an outstanding affinity for soluble hybrid oligosaccharide products of human A and B genes in saliva of heterozygous AB individuals . Neither A nor B salivas, nor an artificial mixture of them, inhibit PA-I hemagglutinating activity to the same extent as saliva from heterozygotes . Other lectins examined do not exhibit this property.

J Biol Chem, 1985 May 10, 260(9), 5518 - 25
A selenomethionine-containing azurin from an auxotroph of Pseudomonas aeruginosa; Frank P et al.; The production and spectroscopic properties of an L-selenomethionine-containing homolog of Pseudomonas aeruginosa azurin are described . The amino acid substitution was carried out by developing an L-methionine-dependent bacterial strain from a fully functional ATCC culture . Uptake studies monitored using L-{75Se}methionine indicated that L-selenomethionine was incorporated into the protein synthetic pathway of Pseudomonas bacteria in a manner analogous to L-methionine . Several batches of bacteria were grown, and one sample of isolated and purified selenoazurin (azurin in which methionine was substituted by selenomethionine) was found (by neutron activation analysis) to contain 5.2 +/- 0.8 seleniums/copper . Correspondingly, a residual 0.35 methionines, relative to 6.0 in the native protein, were found by amino acid analysis in this azurin sample . The redox potential and extinction coefficient of this selenoazurin were found to be 333 +/- 1 mV (pH 7.0, I = 0.22) and 5855 +/- 160 M-1 cm-1 at 626 +/- 1 nm, respectively . Visible electronic, CD, and EPR spectra are reported and Gaussian curve fitting to the former spectrum allowed assignment of the selenomethionine Se----Cu(II) transition to a band found at 18034 cm-1, based upon an observed 450 cm-1 shift to the red from the analogous band position in the native protein . The data are consistent with a relatively more covalent copper site stabilizing the reduced, Cu(I), form in the selenoprotein . A role for the methionine as a modulator of the blue copper site redox potential by metal----ligand back bonding from Cu(I) is discussed in terms of a ligand sphere which limits the valence change at copper to much less than 1 during a redox cycle.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1985 May, 259(3), 397 - 409
Anti-LPS antibody response in Pseudomonas aeruginosa infections . I . Kinetics of the serological response; Petras G et al.; A continuous survey of the serological response in 59 Pseudomonas aeruginosa infections of 30 patients treated in a respiratory intensive care unit revealed that anti-LPS antibody production paralleled the intensity of the infection from the early onset . In lethal cases the immunological response was depressed from the start of the P . aeruginosa complications, probably as a consequence of a too intensive antigenic stimulus exerted by a massive infection . Septic shock was always accompanied by a marked fall in antibody titres . The loss was more expressed in the most effective IgG class antibodies.

Zentralbl Bakteriol Mikrobiol Hyg {B}, 1985 May, 180(5-6), 505 - 14
Mycobacteria in semi-public swimming-pools and whirlpools; Havelaar AH et al.; The presence, densities and species distribution of atypical mycobacteria were assayed in samples from swimming-pools in semi-public areas (hotels, recreational parks and camping grounds) and from whirlpools (in sauna institutes, fitness clubs and recreational parks) . Tap water used to supply these pools was also investigated . Mycobacteria were frequently detected in all types of samples, the numbers in whirlpools on the average being about ten times higher than those in swimming-pools and tap water . Mycobacterium gordonae was the predominant species in all samples . Special attention was given to the possible presence of opportunistic pathogenic mycobacteria . M . marinum was not detected in any of the samples; M . kansasii was recovered 3 times from whirlpools only . M . avium and the M . fortuitum-M . chelonei complex were found in both types of pool samples but in highest densities in whirlpools . Mycobacterial densities exhibited a significantly negative association with the concentration of hypochlorous acid-1.0 mg/l being required to assure low levels in the bathing water . There was also a negative association with redox potential but positive associations with total aerobic colony count at 37 degrees C, ammonium and total Kjeldahl nitrogen (in swimming-pools only) . No association was found with temperature, potassium permanganate consumption, total coliforms, Pseudomonas aeruginosa or Staphylococcus aureus.

J Antimicrob Chemother, 1985 May, 15(5), 597 - 606
Comparative pharmacokinetics and serum bactericidal activity of mezlocillin, ticarcillin and piperacillin, with and without gentamicin; Viollier AF et al.; We compared the serum levels, pharmacokinetics and serum bactericidal activity after intravenous infusions of 5 g of each of three anti-pseudomonal penicillins--ticarcillin, mezlocillin and piperacillin alone and in combination with 80 mg gentamicin in normal volunteers . Gentamicin levels were significantly lower when administered with ticarcillin than when administered with mezlocillin or piperacillin . Serum levels of ticarcillin and piperacillin immediately after the infusion were similar (approximately 450 mg/l) and were higher than mezlocillin at 350 mg/l, but by 6 h, levels of all three penicillins were less than 10 mg/l . Overall, the geometric mean bactericidal titres produced in the serum against organisms which commonly infect cancer patients with granulocytopenia were highest with the piperacillin-gentamicin combination . However, except for the mezlocillin-gentamicin combination against Pseudomonas aeruginosa, serum bactericidal titres of all three penicillin-gentamicin regimes were greater than 1:8 at zero and 2 h after the infusion against the organisms tested . It is unlikely that these differences in the three penicillin-gentamicin combinations will be apparent in the outcome of clinical trials for empiric therapy of fever in the cancer patient with granulocytopenia.

Pathol Biol (Paris), 1985 May, 33(5), 408 - 11
{In vitro study of the effects of a ticarcillin-clavulanic acid combination on Pseudomonas aeruginosa as a function of resistant phenotypes}; Thabaut A et al.; Activity of ticarcillin combined with clavulanic acid against 203 P . aeruginosa strains was studied . 159 strains produced a constitutive beta-lactamase with resistance to ticarcillin (MIC less than 128 mg/l) as a result . Minimal inhibitory concentrations (MICs) were determined using the agar dilution method for ticarcillin alone and combined with 4 and 8 mg/l clavulanic acid . Addition of clavulanic acid failed to change the activity of ticarcillin on ticarcillin-susceptible stains and on strains producing a constitutive cephalosporinase . A synergic effect was demonstrated for PSE and TEM type beta-lactamase producers and for OXA type beta-lactamase producers (4 halving dilutions and 1 to 2 halving dilutions respectively) . However, because of the levels of baseline MICs, the combination brought the MIC of ticarcillin below the cutoff level for a small percentage of PSE strains (6%), moderate percentage of OXA strains (17 to 50%) and significant percentage of TEM strains . These percentages were slightly higher with 8 mg than 4 mg clavulanic acid . Given current data on the prevalence of the various beta-lactamases among resistant strains now being isolated in France, the ticarcillin + clavulanic acid combination will enable to achieve an MIC less than 128 mg/l for 11% (with 4 mg) or 16% (with 8 mg) of resistant strains.

Infection, 1985 May-Jun, 13(3), 125 - 9
Cefotaxime plus amikacin as empiric therapy in the treatment of febrile episodes in neutropenic patients with hematologic malignancies; Martino P et al.; Between October 1980 and October 1981, cefotaxime plus amikacin were used in the treatment of 131 febrile episodes that occurred in 108 neutropenic patients with hematologic malignancies . The overall clinical response was 86.2% . Fevers of unknown origin and clinically or microbiologically documented infections responded in 88.8 and 84.4% of the cases, respectively . Renal toxicity occurred in 3.8% of the cases . In vitro studies showed that cefotaxime and amikacin were active against 78.7 and 94.7% of the pathogens, respectively, despite the high frequency (31%) of multiply resistant strains of Pseudomonas aeruginosa (defined as in vitro simultaneously resistant to carbenicillin, gentamicin, tobramycin and sisomicin) isolated from blood and infected sites . Synergy studies performed against 35 gram-negative bacilli isolated from blood revealed the presence of synergism between cefotaxime and amikacin in 54% of the cases . The peak levels of bactericidal activity in the serum of patients receiving cefotaxime plus amikacin showed median values of 1:128 and 1:8 against Escherichia coli and P . aeruginosa septicemias, respectively.

Zentralbl Bakteriol Mikrobiol Hyg {B}, 1985 May, 180(5-6), 471 - 9
{Pseudomonas aeruginosa in the oral cavity: occurrence and age distribution of adult germ carriers}; Botzenhart K et al.; Among 500 patients of a rural general practice, 4,4% proved to be oropharyngeal carriers of Pseudomonas aeruginosa as shown by examination of mouth rinse fluid through enrichment in malachite-green-broth followed by isolation on Pseudosel-Agar at 42 degrees C . Most positive samples were found in persons 54-63 years old . There were no significant sex differences . The isolation of Ps . aeruginosa showed no relation to visible inflammatory processes in the oral cavity, to dentures, diabetes mellitus, chronic respiratory disease, former antibiotic treatment or smoking habits . The age distribution of the carriers cannot be explained.

Antimicrob Agents Chemother, 1985 May, 27(5), 872 - 3
In vitro activities of Ro 17-2301 and aztreonam compared with those of other new beta-lactam antibiotics against clinical isolates of Pseudomonas aeruginosa; Ng WW et al.; The in vitro activities of Ro 17-2301 and aztreonam against 191 Pseudomonas aeruginosa isolates were compared with those of five other beta-lactam antibiotics . Both compounds showed activities comparable to that of ceftazidime and were bactericidal . They were as effective against gentamicin-or carbenicillin-resistant isolates as against susceptible ones.

Antimicrob Agents Chemother, 1985 May, 27(5), 715 - 9
Five novel plasmid-determined beta-lactamases; Medeiros AA et al.; Five novel plasmid-determined beta-lactamases named TLE-1, OXA-4, OXA-5, OXA-6, and OXA-7 were detected in ampicillin-resistant isolates of Escherichia coli and carbenicillin-resistant strains of Pseudomonas aeruginosa . TLE-1 resembled TEM-1 in substrate profile and reactions with inhibitors but differed in isoelectric point (5.55) and enzyme banding pattern on flat-bed electrofocusing.OXA-4, OXA-5, OXA-6, and OXA-7 hydrolyzed oxacillin, methicillin, and cloxacillin readily but differed from OXA-1, OXA-2, and OXA-3 in substrate profiles, inhibitor reactions, and isoelectric points (7.5 to 7.8).OXA-4 and OXA-6 were unusual for members of the OXA group in their sensitivity to inhibition by cloxacillin . OXA-5 and OXA-7 had isoelectric points close to that of SHV-1, emphasizing the need in beta-lactamase classification for studies in addition to isoelectric focusing . These five new enzymes bring the number of plasmid-determined beta-lactamases known in gram-negative organisms to more than 20 . The evolution of such enzymatic diversity remains to be explored.

J Antimicrob Chemother, 1985 May, 15(5), 633 - 6
Comparative in-vitro activities of azlocillin, ticarcillin and ticarcillin plus clavulanic acid against Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa; Lagast H et al.; Azlocillin (5 g), ticarcillin (5 g) and ticarcillin (5 g) plus clavulanic acid (200 mg) were administered intravenously on separate days to human volunteers . Serum levels 1 h after the infusion were (mean +/- S.E.): 263 +/- 40 mg/1 for azlocillin, 238 +/- 56 mg/l for ticarcillin and 5.5 +/- 1.9 mg/l for clavulanic acid . Serum withdrawn at 0.5 h was titrated against ten strains of Staphylococcus aureus, ten Klebsiella pneumoniae and nine Pseudomonas aeruginosa of which four were resistant to ticarcillin . Against Staph . aureus and K . pneumoniae, median serum bactericidal activity (SBA) and percentage of sera with SBA greater than or equal to 1:8 were greater with ticarcillin plus clavulanic acid (median SBA 1:32 and 85% of sera with SBA greater than or equal to 1:8) than with the other two regimens . There were no differences in activity against Ps . aeruginosa.

J Antimicrob Chemother, 1985 May, 15(5), 579 - 85
Efficacy of rifampicin in experimental Bacteroides fragilis and Pseudomonas aeruginosa mixed infections; Fu KP et al.; Experimental intraabdominal abscesses were produced in mice by intraperitoneal injection of Bacteroides fragilis and Pseudomonas aeruginosa . The therapeutic efficacy of rifampicin and cefsulodin alone, and in combination was investigated in this in-vivo experimental mixed intraabdominal abscess model . Treatment with rifampicin at 10, and 25 mg/kg or cefsulodin at 50, and 100 mg/kg singly or in combinations prevented mortality as compared to 68% mortality rate occurring in the untreated mice . Rifampicin, at 25 mg/kg dose, was very effective in preventing abscess formation and produced bacterial eradication . It prevented abscess formation in 80% of the mice and eradicated both Bacteroides and Pseudomonas in 100% and 75% of the abscesses of the mice . Cefsulodin failed to reduce the incidence of abscess formation, and to eradicate Bact . fragilis from the abscesses, although it significantly decreased Ps . aeruginosa in the abscesses . The combination of rifampicin at 10 mg/kg and cefsulodin at 100 mg/kg was more effective than either of the antibiotics alone and was as effective as rifampicin alone at 25 mg/kg levels . This combination was bactericidal against both organisms in the infected mice.

J Antimicrob Chemother, 1985 May, 15(5), 545 - 9
Comparison of cefpiramide (HR-810) and four anti-pseudomonal beta-lactam agents against pseudomonas isolates from children with cystic fibrosis; Aronoff SC et al.; Cefpiramide (HR-810), ceftazidime, piperacillin, ticarcillin, and aztreonam were tested against tobramycin-sensitive and -resistant strains of Pseudomonas aeruginosa and tobramycin/amikacin-resistant isolates of Ps . cepacia recovered from the sputum of patients with cystic fibrosis . Against Ps . aeruginosa, none of the drugs inhibited 90% of the test strains at levels of less than 128 mg/l . Median minimal, inhibitory concentrations (MIC50) for all of the beta-lactam agents were lower for tobramycin-sensitive versus tobramycin-resistant isolates of Ps . aeruginosa . Ceftazidime was the most effective agent against Ps . cepacia . Aminoglycoside-resistance appears to be associated with significant beta-lactam resistance in Ps . aeruginosa isolated from the sputum of patients with cystic fibrosis.

J Bacteriol, 1985 May, 162(2), 849 - 51
Mutation in Pseudomonas aeruginosa causing simultaneous defects in penicillin-binding protein 5 and in enzyme activities of penicillin release and D-alanine carboxypeptidase; Noguchi H et al.; Penicillin-binding protein 5 in Pseudomonas aeruginosa had moderately penicillin-sensitive D-alanine carboxypeptidase activity . As in Escherichia coli, a defect in this enzyme activity was not lethal.

Infect Immun, 1985 May, 48(2), 498 - 506
Effects of Pseudomonas aeruginosa cytotoxin on human serum and granulocytes and their microbicidal, phagocytic, and chemotactic functions; Baltch AL et al.; The effect of Pseudomonas aeruginosa cytotoxin on human granulocytes (PMNs) and pooled human serum was studied by hemacytometer counts, phagocytic, bactericidal, and chemotaxis assays, and by transmission electron microscopy . The optimal assay conditions for phagocytosis of 75Se-labeled P . aeruginosa 1348A included 20% pooled human serum and a ratio of one PMN to between 10 and 20 bacteria . For the bactericidal assay, 20% pooled human serum and a ratio of one PMN to between one and five bacteria were used . Chemotaxis of PMNs was studied by agarose gel technique with 10(-7) M f-Met-Leu-Phe or 0.01 to 35 micrograms of cytotoxin per ml as a chemoattractant . The degree of PMN destruction was dependent on cytotoxin concentrations and PMN exposure time to cytotoxin . Virtually complete PMN lysis was observed after a 2-h exposure to 6 to 10 micrograms of cytotoxin per ml . PMN exposure to 2 micrograms of cytotoxin per ml for as long as 2 h had no adverse effect on phagocytosis . PMN exposure to greater than or equal to 4 micrograms of cytotoxin per ml for 2 h demonstrated a significant decrease in the percentage of bacteria killed . The results of experiments designed to separate cytotoxin effect on PMN lysis from the effect on PMN bactericidal capacity showed that there is an effect of cytotoxin on PMN bactericidal function . PMN exposure to 4 micrograms of cytotoxin per ml for 30 min caused a significant decrease in PMN migration . Cytotoxin had no chemoattractant qualities or effect on pooled human serum as studied by chemotaxis and phagocytosis assays . Although a cytotoxin concentration of greater than or equal to 2 micrograms/ml was required to demonstrate PMN ultrastructural changes observed in transmission electron microscopy studies, at a concentration of 0.1 microgram/ml, cytotoxin caused an impairment in the integrity of the PMN membrane, allowing a low-molecular-weight substance (ruthenium red) to enter into the cytoplasm . Cytotoxin may be an important factor in the pathogenesis and in the high mortality rate of patients with P . aeruginosa infections.

J Immunol, 1985 May, 134(5), 3089 - 93
Polyclonal B cell stimulation and interleukin 1 induction by the mucoid exopolysaccharide of Pseudomonas aeruginosa associated with cystic fibrosis; Daley L et al.; Mucoid exopolysaccharide isolated from Pseudomonas aeruginosa obtained from colonized cystic fibrosis patients was found to be a potent mitogen for mouse lymphocytes . The responding lymphocyte was a B cell, and we found no evidence that T cell could proliferate or synergize with B cells in response to the mucoid exopolysaccharide . Proliferation was not inhibitable by polymyxin B, which blocks lipopolysaccharide (LPS)-induced proliferation, indicating that a minor LPS contaminant in the purified exopolysaccharide was not the mitogenic component . Mucoid exopolysaccharide induced secretion of IgG, suggesting that it is polyclonal mitogen . It also induced splenic adherent cells (macrophages) to produce interleukin 1 . We propose that mucoid exopolysaccharide produced by P . aeruginosa present in the lungs of cystic fibrosis patients may have potent in vivo consequences resulting in aberrant immunoregulation and inhibition of effective immune elimination of P . aeruginosa.

Pathol Biol (Paris), 1985 May, 33(5), 430 - 4
{Ceftazidime absorption into bronchial secretions in mucoviscidosis patients}; Berthelot G et al.; Penetration of ceftazidime into bronchial secretions was studied in 23 patients, of which 18 had cystic fibrosis . Ceftazidime was used as the single drug for treating exacerbations caused by Pseudomonas aeruginosa . Dosage was 6 g/1.73 m2/day divided into three intravenous injections for 14 to 21 days . Bronchial secretion samples were obtained by fiber-optic bronchoscopy or physical therapy . Serum and bronchial secretion ceftazidime concentrations were assayed using a microbiological method . Ceftazidime concentrations in both media were lower in children than in adults : elimination half-life is shorter (1.7 h against 2.45 h in adults), extravascular distribution is faster, with earlier (1 h against 2 h in adults) achievement of the peak bronchial secretion concentration (2 micrograms/ml) . The ratio of bronchial secretion concentration to concomitant serum concentration did not exceed 5% at the time of peak bronchial concentration . These results suggest that in cystic fibrosis patients, the faster and lower bronchial penetration of ceftazidime may be due to faster elimination as compared to adults . Although transient elimination of Pseudomonas aeruginosa was achieved in 12 study patients, our findings support the use of higher dosages or alternative administration modalities designed to increase in situ ceftazidime concentrations.

Clin Pharm, 1985 May-Jun, 4(3), 316 - 20
Twice-daily moxalactam versus gentamicin and clindamycin in patients with penetrating abdominal trauma; Crots LD et al.; The effectiveness and total costs of moxalactam administered every 12 hours versus a combination of gentamicin and clindamycin for prophylactic use in patients with penetrating abdominal trauma were compared . Fifty patients scheduled for laparotomy after penetrating abdominal wounds were randomly assigned to receive either clindamycin phosphate 600 mg every six hours with gentamicin (as the sulfate salt) 3-5 mg/kg/day in three divided doses or moxalactam disodium 2 g every 12 hours . Therapy was begun preoperatively and continued for a minimum of three days in patients without hollow-organ injury and five days in patients with hollow-organ injury; total duration of therapy could not exceed four weeks . Patients receiving moxalactam also received phytonadione 10 mg intramuscularly once a week . Although wound cultures from several patients were positive for Staphylococcus epidermidis, Pseudomonas aeruginosa, and enterococci, no symptomatic infections developed . No direct toxic effects of moxalactam or gentamicin-clindamycin were seen; transient abnormalities in blood-coagulation tests or serum creatinine concentration occurred in several patients . Although mean drug costs per patient for moxalactam and gentamicin-clindamycin were similar, the mean cost of therapy per patient was $125.23 higher for the combination regimen than for moxalactam when laboratory, personnel-time, and supply costs were added to drug costs . Moxalactam given every 12 hours was a safe and effective alternative to the combination of gentamicin and clindamycin for preventive use in the study patients with penetrating abdominal trauma.

Genetika, 1985 May, 21(5), 735 - 47
{Characteristics of phages-transposons of Pseudomonas aeruginosa belonging to 2 groups distinguished by DNA-DNA homology}; Akhverdian VZ et al.; 14 new transposable phages (TP) were isolated from approx . 200 clinical isolates of Pseudomonas aeruginosa . The frequent occurrence of TP of P . aeruginosa has been confirmed . There are at least two different groups of TP, namely, the group of D3112 and that of B3 . The distinctive features of phages belonging to the groups are as follows: 1) low level of DNA-DNA homology (less than 10%), the whole region of homology in phage genomes of different groups being located on right genome end (29-38 kb); only one of phages of the B3 group shows an additional homology with D3112 DNA outside the above mentioned region; 2) a variable DNA is observed on the left end of the B3 group phage genomes and no such DNA is revealed on the left end of genomes of the D3112 group phages; 3) all phages of the B3 group have specific type of interaction with RPL11 plasmid, which distinguish them from phages of the D3112 group; 4) phages belonging to the two groups differ greatly in their growth in cells harbouring pMG7 plasmid which mediates production of PaeR7 endonuclease and in the number of DNA sites sensitive to SalGI, PstI, BglII endonucleases . Since some of the B3 group phage genomes possess BamH1 sites, resistance to this enzyme cannot be regarded as a general characteristics for all TP of P . aeruginosa, as it was earlier proposed . Some aspects of modular hypothesis of bacteriophage evolution concerning, in particular, the ways of module formation are discussed.

Genetika, 1985 May, 21(5), 724 - 34
{Modular structure of the genes of phages-transposons of Pseudomonas aeruginosa}; Krylov VN et al.; The basic criterion to confirm the recombinational origin of bacteriophages belonging to the same phage family is revealing several different combinations of differentiated segments in phage genomes which determine specific functions (modules) . The results of phage-to-phage comparison of several regions in genomes of closely related transposable phages of Pseudomonas aeruginosa D3112, B39, PH2, PH51, PH93, PH132 have supported the modular hypothesis for this group of phages.

FEBS Lett, 1985 Apr 22, 183(2), 408 - 12
Cloning and sequencing of the Pseudomonas aeruginosa PAK pilin gene; Pasloske BL et al.; A 1.2-kilobase (kb) HindIII restriction fragment containing the pilin gene from Pseudomonas aeruginosa PAK has been cloned and sequenced . The pilin protein is 144 amino acids in length with a positively charged leader sequence of 6 amino acids . There is probably only one copy of the gene per chromosome.

Biochim Biophys Acta, 1985 Apr 5, 828(2), 138 - 43
Circular dichroism of diphtheria toxin, Pseudomonas aeruginosa exotoxin A, and various derivatives; Collins CM et al.; We have recorded the near- and far-ultraviolet circular dichroism spectra of diphtheria toxin, Pseudomonas aeruginosa exotoxin A, and derivatives of these toxins . The far-ultraviolet spectra of various forms of diphtheria toxin were virtually identical, implying that no major changes in secondary structure accompany proteolytic nicking or dimerization of toxin, or binding of the endogenous dinucleotide, adenylyl-(3'-5')-uridine 3'-monophosphate (AdoPUrdP) . Alpha-helix content was estimated to be 29%, as compared with 8% for fragment A . Near-ultraviolet spectra were identical between nicked and intact diphtheria toxin . A broad negative transition with a minimum at 304 nm was assigned to the intrachain disulfide bridge within the B moiety . Dimeric diphtheria toxin showed perturbations of aromatic residues . Binding of AdoPUrdP to monomeric diphtheria toxin or of adenylyl-(3',5')-uridine (AdoPUrd) to fragment A perturbed one or more tryptophans . The latter results correlate with evidence for involvement of a tryptophan in NAD binding . Native exotoxin A was estimated to have 16% alpha-helix, and the activated form of exotoxin A, 11% . An enzymically active, 31 kDa proteolytic fragment of exotoxin A showed similar alpha-helix content (7%) to that of diphtheria toxin fragment A.

Infect Immun, 1985 Apr, 48(1), 57 - 61
Modulation of pulmonary clearance of bacteria by antioxidants; Pesanti EL et al.; To further delineate the mechanisms underlying murine pulmonary defenses against bacterial infection, we studied the effects of antioxidant enzymes and hydroxyl radical scavengers on pulmonary clearance processes . Intratracheal injection of catalase and superoxide dismutase resulted in prolonged intraalveolar residence of the enzymes, but caused no decrease in rates of clearance of either Staphylococcus aureus 502A or Pseudomonas aeruginosa PAO1 . In contrast, dimethylsulfoxide and dimethylthiourea caused significant depression of clearance of P . aeruginosa without altering clearance of S . aureus . These results provide further differentiation between clearance processes affecting gram-negative and gram-positive bacteria and suggest that murine clearance of gram-negative organisms may be in part mediated by reactions which generate hydroxyl anion . In vivo administration of agents which inhibit hydrogen peroxide-, superoxide-, or hydroxyl anion-mediated reactions do not alter normal clearance of S . aureus.

Jpn J Antibiot, 1985 Apr, 38(4), 1022 - 8
{In vitro combination effects of astromicin and beta-lactam antibiotics against Pseudomonas aeruginosa . In vitro synergistic activities}; Iyama Y et al.; In vitro synergistic activities of astromicin (ASTM), a new aminoglycoside antibiotic, combined with beta-lactam antibiotics (cefsulodin (CFS), cefoperazone (CPZ), latamoxef (LMOX) were investigated against P . aeruginosa by the checkerboard technique, FIC index and the killing curve . FIC indexes of ASTM in combination with beta-lactam antibiotics against 11 fresh clinical isolates of P . aeruginosa, P . aeruginosa BMH No . 1 and E-2 were synergistic or partially synergistic in most cases . Checkerboard of P . aeruginosa BMH No . 1 and E-2 to ASTM and 3 beta-lactam antibiotics showed the synergism, too . Bacteriostatic concentrations of ASTM, CFS, CPZ or LMOX showed synergistically bactericidal effects when these antibiotics were added in combination to the culture of P . aeruginosa BMH No . 1.

Nippon Seikeigeka Gakkai Zasshi, 1985 Apr, 59(4), 429 - 41
{An experimental study on pyogenic osteomyelitis with special reference to polymicrobial infections}; Hidaka S; The author used the following method to successfully devise a model of experimental osteomyelitis caused by two different bacteria . A 3-mm silk thread (No . 5) soaked in Staphylococcus aureus (1.0 X 10(4) CFU) and Pseudomonas aeruginosa (1.0 X 10(5) CFU) suspensions was dried under reduced pressure . The silk thread was inserted into the metaphysis of the right tibia of mice . Experimental osteomyelitis caused by these two species of bacteria was successfully produced in all the mice, and this infection was similar to osteomyelitis in man . After prior infection with S . aureus, P . aeruginosa (1.0 X 10(3) CFU) was inoculated directly into the tibia of mice during the acute and chronic stages of the S . aureus infection, and secondary infection by P . aeruginosa was confirmed in all the mice . Using this experimental model of osteomyelitis, the author administered an antibiotic that is effective against only S . aureus in mice and observed abrupt growth of P . aeruginosa to elucidate certain aspects of the bacterial replacement phenomena.

Acta Pathol Microbiol Immunol Scand {B}, 1985 Apr, 93(2), 157 - 8
Pressure- and temperature-dependent adhesion of Pseudomonas aeruginosa to HEp-2 cells; Berdal BP et al.; Pseudomonas aeruginosa bacteria adhere to human epitheloid (HEp-2) cells in culture . Under normal atmospheric conditions (1 ATA), this adhesion increased significantly when the temperature rose from 22 to 37 degrees C . Under hyperbaric atmosphere (= air, 7 ATA) conditions, a similar, significant enhancement of bacterial adhesion to the cells was noted when the temperature rose . If the temperature was kept stable at 22 or 37 degrees C and the pressure was increased from 1 to 7 ATA, a pressure-induced enhancement was observed . This was statistically significant, at both temperature levels . Temperature-induced or -stimulated adhesion may help to explain some outbreaks of P . aeruginosa infections, for instance in whirlpools . The enhancement of this phenomenon under hyperbaric atmosphere conditions could have some relevance to recurrent P . aeruginosa otitis externa, a most common nuisance among professional divers.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1985 Apr, 259(2), 201 - 5
Resistance patterns of nonfermentative gram-negative rods and aeromonads to beta-lactam antibiotics: a diagnostic aid; von Graevenitz A et al.; Consistent resistance to certain antimicrobial agents has in the past been of help in the diagnosis of nonfermentative gram-negative rods . In order to establish patterns of consistent resistance to 15 mostly newer betalactam antibiotics, 561 strains of such organisms plus Aeromonas and Plesiomonas were tested with the Kirby-Bauer method and also against the selective agent C-390 in three concentrations in Mueller-Hinton agar . No species-specific patterns emerged but the resistance data can be used to exclude certain species . C-390 was almost specifically selective for Pseudomonas aeruginosa.

Genetika, 1985 Apr, 21(4), 548 - 55
{Complementation and the physiological characteristics of the ts mutants of Pseudomonas aeruginosa phage SM}; Gorelyshev AS et al.; Seventy three temperature-sensitive mutants of Pseudomonas aeruginosa SM phage have been obtained using different mutagens and assigned to thirteen complementation groups . Representative mutants of each group have been studied with the aim of characterizing tentatively the time of genes expression in infected bacteria . Two genes appear to function during the first minutes after infection, whereas the remaining genes are needed for late functions . Most of the temperature-sensitive functions in the different mutants are reversible, i.e . they become active when the infected cells are shifted-down to the permissive temperature.

Eur J Clin Microbiol, 1985 Apr, 4(2), 219 - 23
Twenty-five year review of Pseudomonas aeruginosa bacteremia in a burn center; McManus AT et al.; The incidence of Pseudomonas aeruginosa bacteremia was examined in 5,882 burn patients consecutively admitted over a 25-year period to one burn center . The population examined had an average burn size of 33.8% of the body surface and an average age of 26.3 years . Pseudomonas aeruginosa bacteremia occurred in 540 patients . These patients had an average burn size of 54.2% and average age of 28 years . Mortality was 77% . Bacteremia with other organisms occurred during hospitalization of all but 128 of the 540 patients . Comparison of predicted mortality based on burn size and age to observed mortality showed Pseudomonas aeruginosa bacteremia to be associated with a 28% increase in mortality . Examination of mortality as a function of time showed no significant change over the 25-year period . The incidence of Pseudomonas aeruginosa colonization and infection was examined in 400 recently admitted burn patients . Colonization occurred in 107 and 34 infections were recorded in 27 of the colonized patients.

Eur J Clin Microbiol, 1985 Apr, 4(2), 207 - 12
Use of discriminative models of Pseudomonas aeruginosa bacteremia in granulocytopenic rats for testing antimicrobial efficacy; Johnson D; The efficacy of single agent and combination antibiotic therapy was evaluated in rats with severe granulocytopenia and Pseudomonas aeruginosa infection using animal survival, rates of bacteremia and the emergence of resistant organisms as criteria . In this model end points following single agent therapy with imipenem/cilastatin and the synergistic combination of moxalactam plus amikacin were comparable . At a high bacterial challenge dose, equivalent results were obtained using single agent therapy with either piperacillin or ticarcillin . Results were also similar following therapy with piperacillin or ticarcillin in synergistic combination with amikacin . At a lower bacterial challenge dose, aminoglycoside therapy was superior to therapy with the beta-lactams . Therapy with the in vitro synergistic double beta-lactam combination of ceftazidime plus piperacillin was no more effective than therapy with the individual compounds . Results from these studies in this discriminative animal model have in part been used to formulate prospective clinical antibiotic studies in granulocytopenic cancer patients.

Eur J Clin Microbiol, 1985 Apr, 4(2), 201 - 6
Reaction of antibody in sera from cystic fibrosis patients with non-toxic forms of Pseudomonas aeruginosa exotoxin A; Klinger KW et al.; Sera from 48 cystic fibrosis patients from two hospitals were screened for antibody against rods, non-toxic macromolecular structures which share antigenic determinants with Pseudomonas aeruginosa exotoxin A . A solid-phase radioimmunoassay employing (125I)-staphylococcal protein A was used to detect anti-rod IgG . Antibodies recognizing rods, exotoxin A, or both antigens, were demonstrated using a competitive radioimmunoassay in cystic fibrosis patient sera, and in sera from animals immunized with exotoxin A, rods, or infected with Pseudomonas aeruginosa . Anti-rod titers of cystic fibrosis patients (1.07 to 14 X control serum levels) inversely correlated with aggregate clinical evaluation scores, and in most instances, with X-ray scores . Since rods are non-toxic and cross-reactive with exotoxin A, they may represent therapeutically useful antigens for producing immunity to exotoxin A.

Eur J Clin Microbiol, 1985 Apr, 4(2), 197 - 200
Enzyme-linked immunosorbent assay for detection of antibodies to Pseudomonas aeruginosa exoproteins; Granstrom M et al.; Enzyme-linked immunosorbent assays were developed with four purified Pseudomonas aeruginosa extracellular proteins (exotoxin A, elastase, alkaline protease, and phospholipase C) to determine antibody levels in sera from healthy subjects and the serological response in patients colonized or infected with Pseudomonas aeruginosa . Five of 39 burn patients with wounds colonized by Pseudomonas aeruginosa had elevated antibody titers to alkaline protease . Response to the other antigens was found in only a few patients . Pseudomonas aeruginosa infections (septicemia, osteitis, pneumonia etc.) resulted in increased antibody levels to exotoxin A or phospholipase C in 15 of 22 patients . These findings suggest that repeated determinations of antibodies to Pseudomonas aeruginosa exotoxin A and phospholipase C might be used to monitor therapy in certain patients with osteitis and other deep Pseudomonas infections.

Eur J Clin Microbiol, 1985 Apr, 4(2), 190 - 6
Evaluation of three serological tests for detection of antibody to Pseudomonas aeruginosa in human sera; Pitt TL et al.; Four hundred and ninety-five sera from 325 patients from whom Pseudomonas aeruginosa had been isolated and 86 control sera were tested for antibody by indirect haemagglutination tests (HAT) and complement fixation tests (CFT) using a polyvalent pseudomonas serotype-specific vaccine antigen, PEV-02 . Sera were also tested by countercurrent immunoelectrophoresis (CIE) for precipitins to a species-specific protein antigen . Control sera gave titres of 160 or less by HAT and 20 or less by CFT . 2-Mercaptoethanol resistant antibody titres (immunoglobulin G) were below 40 for all control sera and none of the latter contained precipitins to common antigen . Of 325 patients, 156 (48%) gave titres of 320 or greater by HAT and of these, 114 (73%) showed elevated immunoglobulin G titres . Less patients with positive blood cultures than expected were positive by HAT and more patients with bone infections gave raised immunoglobulin G titres than expected . Cystic fibrosis patients were invariably seropositive by all tests . There was a correlation between positive CIE and CFT tests, especially in patients who were positive by HAT . Approximately half of 83 patients tested gave a serotype-specific antibody response . The tests were of little value in confirming clinically evident acute infections, but in cases of doubtful infection they did provide confirmatory evidence of an antibody response in approximately one-third of patients culture-positive for Pseudomonas aeruginosa.

Eur J Clin Microbiol, 1985 Apr, 4(2), 186 - 9
Prophylaxis of Pseudomonas aeruginosa infections in leukopenic mice by a combination of active and passive immunization; Martinez D et al.; Mice rendered leukopenic with cyclophosphamide and then challenged with viable Pseudomonas aeruginosa were used to determine the protective efficacy of active immunization against exotoxin A and of passive immunization with human antiserum to Escherichia coli J5, a rough mutant of Escherichia coli O111:B4 . Neither treatment alone provided a greater degree of protection than its respective control . However, the combination of these treatments produced a moderate, yet consistent, increase in the survival of infected immunosuppressed mice.

Eur J Clin Microbiol, 1985 Apr, 4(2), 160 - 2
Further characterization of the tracheal receptor for Pseudomonas aeruginosa; Ramphal R et al.; The purpose of this study was to obtain more information on the nature of the macromolecule to which Pseudomonas aeruginosa adheres . Acid-injured tracheal epithelium was treated with trypsin or lipase to determine whether the receptor molecule was a protein or a lipid . Lipase treatment significantly reduced adherence to these cells, whereas trypsin had no effect . Since the receptor appeared to be a lipid containing sialic acid, gangliosides were used to test whether they would inhibit adherence . Crude ganglioside preparations inhibited adherence in a dose-dependent manner when added to the bacteria before exposure to tracheal cells . Lastly, fibronectin, which presumably binds to gangliosides, significantly reduced the adherence of these organisms . According to these findings Pseudomonas aeruginosa appears to adhere to a sialic acid-containing glycolipid on cell surfaces, probably a ganglioside.

Can J Microbiol, 1985 Apr, 31(4), 377 - 80
Virulence of Pseudomonas aeruginosa strains with mechanisms of microbial persistence for beta-lactam and aminoglycoside antibiotics in a mouse infection model; Bryan LE et al.; A series of mutations and transductants producing low-level aminoglycoside and beta-lactam antibiotic resistance of Pseudomonas aeruginosa have been constructed in an isogenic background . The phenotypes of these mutations are identical to or closely resemble those of clinical isolates of P . aeruginosa associated with therapeutic failure or microbial persistence in the presence of members of one or both groups of drugs . Virulence of the mutants was examined in an infection model using iron-dextran treated mice and bacteria grown in low-iron medium . All beta-lactam resistant mutants affecting affinity of penicillin-binding proteins for beta-lactams, constitutive beta-lactamase, or permeability of beta-lactams retained parental levels of virulence . Aminoglycoside-resistant mutants with defective energy generation or transductants with modified lipopolysaccharide showed reduced virulence . Strains with the preceding forms of resistance are likely to account for therapeutic failure or microbial persistence with antibiotic treatment . We propose that mechanisms of low or unstable forms of resistance should be designated mechanisms of persistence to differentiate them from more classical mechanisms of resistance.

Burns Incl Therm Inj, 1985 Apr, 11(4), 252 - 8
Enzyme-linked immunosorbent assay (ELISA) and a passive haemagglutination test (PHT) for the detection of pseudomonas antibodies in burned patients; Roe EA et al.; Pseudomonas antibodies were measured in serial plasma samples from patients with burns using an enzyme-linked immunosorbent assay (ELISA), passive haemagglutination test (PHT) and a passive protection test (PPT) . ELISA and PHT showed that from 7 days after burning, 15 patients immunized with a 16-part polyvalent vaccine had higher titres of antibody to the 16 antigens in the vaccine than 15 unvaccinated patients . There was evidence that ELISA and PHT detected different pseudomonas antibodies in the plasma samples . When a single antigen (type 6) from the polyvalent vaccine was used in ELISA it failed to monitor antibodies in the plasma from vaccinated and unvaccinated burned patients shown by a PPT to protect mice against Pseudomonas aeruginosa serotype 6 . PHT gave a closer correlation of protective antibodies against type 6 antigen than ELISA.

Antimicrob Agents Chemother, 1985 Apr, 27(4), 468 - 72
Selective inhibition of the accumulation of extracellular proteases of Pseudomonas aeruginosa by gentamicin and tobramycin; Warren RL et al.; Gentamicin and tobramycin inhibited the accumulation of extracellular proteases secreted by Pseudomonas aeruginosa . The secretion of protease was inhibited at concentrations of these drugs that were below the level required to inhibit general protein synthesis . Neither magnesium ions nor high ionic strength antagonized the ability of the aminoglycosides to block secretion of the proteases . Under these culture conditions magnesium ions were shown to antagonize the effects of the aminoglycosides on protein synthesis and aminoglycoside-mediated lysozyme lysis of P . aeruginosa . These results suggested that the drugs blocked secretion of the proteases by acting at the level of the outer membrane.

J Am Acad Dermatol, 1985 Apr, 12(4), 662 - 8
Occlusive wound dressings to prevent bacterial invasion and wound infection; Mertz PM et al.; This study was designed to examine the possibility that some occlusive dressings are barriers to wound penetration by pathogenic bacteria . Two common skin pathogens, the nonmotile, Staphylococcus aureus, and the motile, Pseudomonas aeruginosa, were used to challenge dressings placed on partial-thickness wounds in swine . S . aureus was recovered from 100% of air-exposed wounds (log, 5.5 +/- 1.1) and from 50% of Op-Site-treated and Vigilon-treated wounds (log, 6.1 +/- 1.1) . S . aureus was not isolated from DuoDERM-covered wounds . P . aeruginosa was recovered from 100% of air-exposed wounds (log, 5.1 +/- 0.5) and 100% of Op-Site-covered and Vigilon-covered wounds (log, 5.8 +/- 1.8) . P . aeruginosa was not recovered from DuoDERM-covered wounds . These studies lend support to the idea that dressings may protect wounds from invasion by pathogenic bacteria and demonstrate the need to evaluate their bacterial barrier properties in situ.

J Infect Dis, 1985 Apr, 151(4), 589 - 98
IgG proteolytic activity of Pseudomonas aeruginosa in cystic fibrosis; Fick RB Jr et al.; To study how fragmented IgG antibodies might arise within the respiratory secretions of individuals with cystic fibrosis (CF), we screened protease extracts from CF polymorphonuclear leukocytes and mucoid and nonmucoid transformants of Pseudomonas aeruginosa from patients with CF for IgG proteolytic activity . All strains of P . aeruginosa tested exhibited IgG proteolytic activity . Incubation for 7 hr at 37 C was required to demonstrate generation of free Fc gamma immunoreactivity . Further analysis of these cleavage products of CF IgG demonstrated generation of Fc gamma polypeptides with 4S sedimentation coefficients and F(ab')2 fragments with 5S coefficients . Bacterial IgG proteolytic activity was inhibited by EDTA and was associated with levels of bacterial elastase exceeding 5 micrograms/mg of total protein . Pseudomonas elastase was significantly more active on IgG1 and IgG3; IgG2 and IgG4 were more resistant . This bacterial exoproduct appears to digest IgG molecules into Fab gamma, F(ab')2 fragments, and a free Fc gamma piece with a molecular weight of 40,000.

J Infect Dis, 1985 Apr, 151(4), 581 - 8
Studies on the ability of alginate to act as a protective immunogen against infection with Pseudomonas aeruginosa in animals; Woods DE et al.; Most patients with cystic fibrosis become colonized and infected with mucoid Pseudomonas aeruginosa . The major component of the mucoid material has been identified as the polysaccharide alginic acid . The present work was undertaken to determine whether antibody to alginate is protective in a model of chronic lung infection with P . aeruginosa in rats . Bacterial clearance was associated with a rise in titers of antibody to alginate . In a number of animals a rise in antibody titers was not seen, and in fact a decrease was noted at 30 days compared with 10 days . This observation suggested the possibility of immune complex formation due to antigen excess . Evidence for immune complex deposition in tissues was obtained by immunofluorescence studies . Thus antibody to alginate may offer strain-dependent protection against chronic lung infection with P . aeruginosa in rats; however, immune complex formation should be considered as a possible consequence of immunization with alginate.

J Cell Physiol, 1985 Apr, 123(1), 64 - 72
Pseudomonas aeruginosa cytotoxin stimulates prostacyclin production in cultured pulmonary artery endothelial cells: membrane attack and calcium influx; Suttorp N et al.; The effects of highly purified Pseudomonas aeruginosa cytotoxin were investigated on cultured pulmonary artery endothelial cells . This toxin dose-dependently (7.5-60 micrograms/ml) and time-dependently (20-75 minutes) stimulated the release of radiolabeled arachidonic acid and metabolites and the synthesis of prostacyclin in the absence of overt cell damage (no enhanced lactate dehydrogenase {LDH} release) . Preincubation of the toxin with neutralizing antibodies abolished the effect . The toxin response on endothelial cells required extracellular calcium but not magnesium and was accompanied by a calcium influx . Interference with intracellular calcium function by TMB 8 or with (calcium)-calmodulin function by trifluoperazine and W7 dose-dependently reduced the cytotoxin mediated synthesis of prostacyclin . Calcium channel blockers (nimodipine, diltiazem, verapamil, D 888), however, were ineffective in this system . Following addition of cytotoxin to endothelial cells, an increased passive permeability for small marker molecules (potassium, 45calcium, 3H-sucrose), but for large ones (3H-inulin, 3H-dextran, LDH) was noted, suggesting that cytotoxin creates discrete hydrophilic transmembrane lesions of about 0.5-1.5 nm in diameter . These data are compatible with the notion that Pseudomonas aeruginosa cytotoxin triggers the arachidonic acid pathway in cultured pulmonary artery endothelial cells by calcium influx and suggest that this calcium influx may proceed through toxin created transmembrane lesions.

Acta Pathol Microbiol Immunol Scand {B}, 1985 Apr, 93(2), 105 - 12
Frequency of Aspergillus fumigatus isolates and antibodies to aspergillus antigens in cystic fibrosis; Schonheyder H et al.; The frequency of Aspergillus fumigatus isolates from sputum was assessed prospectively during a 22-month period in 156 patients with cystic fibrosis (CF) from one center, and findings were compared to a cross-sectional evaluation of specific IgG and IgA antibodies, occurrence of chronic Pseudomonas aeruginosa infection, and pulmonary function . The prevalence rate for the 22-month period was 40% . Positive A . fumigatus cultures appeared to be independent of the presence or duration of chronic bronchopulmonary Ps . aeruginosa infection, but isolation of A . fumigatus in patients with pseudomonas infection for more than 5 years was associated with notably decreased pulmonary function . Levels of IgG antibodies to a 470,000 daltons A . fumigatus antigen fraction were higher in patients with positive cultures in the observation period than in those without . IgG antibodies to a 25,000-50,000 daltons antigen fraction were directly correlated to A . fumigatus frequency in patients with positive cultures both prior to and during the survey . On the other hand, levels of IgA antibodies to the 470,000 daltons fraction were inversely related to A . fumigatus frequency, suggesting a role of IgA antibodies in the bronchial clearance of aspergilli . Decreased pulmonary function was found to be associated with elevated levels of A . fumigatus antibodies . It is concluded that immune reactions elicited by A . fumigatus may play a role in clearance of the fungus from the airways but also may contribute to lung morbidity in some patients.

Eur J Clin Microbiol, 1985 Apr, 4(2), 156 - 9
Evolving epidemiology of Pseudomonas aeruginosa infections; Cross AS; The dramatic increase in infections caused by Pseudomonas aeruginosa over the last three decades is examined in this review . By virtue of its unique growth characteristics, this organism occupies a firm niche in the hospital environment where it continues to be a major nosocomial pathogen, with particularly high rates of infection in traditionally susceptible patient subpopulations: the compromised host, patients with malignancy, cystic fibrosis, burn wounds and trauma . In recent years infection with Pseudomonas aeruginosa has become more prominent in other patient subpopulations: for example, post-surgical, pediatric and dialysis patients, as well as the elderly . A more interesting evolution in the epidemiology of infections caused by Pseudomonas aeruginosa is the appearance, often anecdotal, of new manifestations in healthy, non-hospitalized hosts e.g . the water-associated syndromes, puncture wounds, drug addiction . The need for better data on the prevalence of these infections, the required host-organism interactions and their practical impact sets an agenda for future investigation.

Antimicrob Agents Chemother, 1985 Apr, 27(4), 452 - 4
Activities of pefloxacin and ciprofloxacin in experimentally induced Pseudomonas pneumonia in neutropenic guinea pigs; Gordin FM et al.; Pefloxacin and ciprofloxacin are two new quinoline carboxylic acid derivatives that have activity in vitro against a wide range of gram-negative bacteria, including Pseudomonas aeruginosa . Using a well-standardized model of Pseudomonas pneumonia in neutropenic guinea pigs, we tested the efficacy in vivo of these new agents . Both were highly effective in increasing survival and decreasing bacterial counts in the lungs of surviving animals . Pefloxacin and ciprofloxacin were significantly better (P less than 0.05) than aminoglycosides or beta-lactams tested in prior studies with this model, and they were as effective as combination therapy with aminoglycosides and beta-lactams . Resistance to either ciprofloxacin or pefloxacin did not emerge during the study period . Further studies with these drugs in the therapy of Pseudomonas sp . infections are warranted.

Infect Immun, 1985 Apr, 48(1), 130 - 8
Siderophore activity of pyoverdin for Pseudomonas aeruginosa; Cox CD et al.; Pseudomonas aeruginosa produces an extracellular compound with yellowish green fluorescence, called pyoverdin, which functions as a siderophore . The production of pyoverdin, formerly called fluorescein, is concomitant with the production of another siderophore, pyochelin . Pyoverdin is produced by P . aeruginosa in several forms, some of which were separated on gel filtration columns and on reverse-phase, high-pressure liquid chromatography columns . An active form of iron-free pyoverdin was purified to homogeneity . The elution of pyoverdin from the columns was monitored for absorbance, fluorescence, and siderophore activities . These activities, iron binding, and the stimulation of bacterial iron transport indicated that pyoverdin can function as a siderophore for P . aeruginosa . The siderophore function of pyoverdin may be related to the pathogenicity of this bacterium because pyoverdin stimulated growth not only in iron-deficient culture medium, but also in defined medium containing transferrin and in human serum or plasma.

Eur J Clin Microbiol, 1985 Apr, 4(2), 175 - 9
Role of exoenzyme S in chronic Pseudomonas aeruginosa lung infections; Nicas TI et al.; Exoenzyme S is an extracellular ADP-ribosyltransferase enzyme produced by Pseudomonas aeruginosa . Mutants of Pseudomonas aeruginosa deficient in this enzyme have been shown to have reduced virulence in infections of burned mice . The contribution of exoenzyme S to the pathogenesis of chronic lung infections with this organism was evaluated by examining the incidence of exoenzyme S production by Pseudomonas aeruginosa strains isolated from cystic fibrosis patients and comparing an exoenzyme S deficient mutant and its exoenzyme S producing parent in a rat chronic lung infection model . Of 51 isolates examined, 43% produced detectable levels of exoenzyme S . While both the exoenzyme S deficient mutant and its parent strain were equally capable of colonizing and persisting in rat lungs, the exoenzyme S producing parent elicited a greater degree of lung damage . These data suggest that exoenzyme S contributes to the pathogenesis of chronic lung infections.

Eur J Clin Microbiol, 1985 Apr, 4(2), 163 - 9
Use of transposon mutants to assess the role of exoenzyme S in chronic pulmonary disease due to Pseudomonas aeruginosa; Woods DE et al.; Among the potential virulence factors produced by Pseudomonas aeruginosa there are two distinct ADP-ribosyl transferases, exotoxin A and exoenzyme S . The role of exoenzyme S in Pseudomonas aeruginosa infection was studied using the rat chronic pulmonary infection model . Pseudomonas aeruginosa strain DG1 and an isogenic mutant of DG1 differing only in its capacity to produce exoenzyme S were employed in the study . Both Pseudomonas aeruginosa strains tested established a chronic pulmonary infection in this model and organisms recovered from lung homogenates were phenotypically unaltered with respect to exoenzyme S production in vitro . The extent of the observed pathology was markedly greater with the strain producing exoenzyme S, indicating that exoenzyme S may play a role in the progressive pathology observed in chronic lung disease due to Pseudomonas aeruginosa.

Can J Microbiol, 1985 Apr, 31(4), 387 - 92
The contribution of exoproducts to virulence of Pseudomonas aeruginosa; Nicas TI et al.; Pseudomonas aeruginosa produces a large number of extracellular products which may contribute to its virulence . We have employed a genetic approach to determine the contribution of toxin A, exoenzyme S, elastase and alkaline protease to the pathogenesis of P . aeruginosa . Mutations have been introduced with chemicals or transposons . Mutants have been identified using immunological, chemical, or toxicity assays . Mutants were extensively characterized in vitro to ascertain that they were identical to their parent strain except for the production of the desired product . Appropriate mutants were compared with their parent strains in several animal models: the burned mouse model, the mouse corneal infection model, and a rat model of chronic lung infection . The data indicate that virulence of P . aeruginosa is multifactorial . Further, the relative contribution of a given P . aeruginosa product may vary with the type of infection.

J Clin Invest, 1985 Apr, 75(4), 1230 - 7
Isolation and partial characterization of a human alveolar macrophage-derived neutrophil-activating factor; Pennington JE et al.; Human alveolar macrophages (AM) were obtained from eight normal volunteers using fiberoptic bronchoscopic lavage to explore potential interrelationships among leukocytes in pulmonary defense against infection . AM placed in monolayer tissue cultures released material into culture supernatants with the capacity to enhance the bactericidal capacity of human neutrophils . Neutrophils preexposed to supernatants killed Pseudomonas aeruginosa from 70 to 90% more efficiently than control cells (P less than 0.02) . AM culture supernatants contained this material by 4 h of incubation, and in vitro stimulation of AM cultures with heat-killed P . aeruginosa further increased its production . Gel filtration of AM culture supernatants with a G-50 Sephadex column allowed isolation of a 6,000-D neutrophil-activating factor (NAF) that was resistant to heat (56 degrees C, 30 min) . The isoelectric point of NAF, as determined by chromatofocusing, was approximately 7.6 . Enzyme digestion of NAF specimens, prepared sequentially by gel filtration and chromatofocusing, demonstrated 50-70% loss of activity after incubations with trypsin, chymotrypsin, and neuraminidase . NAF was only minimally chemotactic and eluted from Sephadex G-50 with particles of a different molecular size than those of AM-derived chemotactic factors (i.e., approximately 10,000 D and less than 500 D) . Preincubation of neutrophils with NAF resulted in greater release of superoxide anion upon their subsequent stimulation by either bacterial phagocytosis or by phorbol myristate acetate, as compared with control neutrophils stimulated in a like manner . These studies indicate that human AM secrete a heat-stable, low molecular weight basic protein, with the capacity to enhance oxidative microbicidal activity of neutrophils.

Proc Natl Acad Sci U S A, 1985 Apr, 82(7), 2039 - 43
1H NMR studies of electron exchange rate of Pseudomonas aeruginosa azurin; Ugurbil K et al.; T1 values of the His-35 C-2 proton resonance of reduced Pseudomonas aeruginosa azurin were determined at 25 degrees C and pH values 4.5, 7.3, and 9.0 in the presence of different fractional amounts of oxidized azurin . The C-2 proton of His-35 undergoes very rapid spin relaxation in oxidized azurin because of its close proximity to the paramagnetic copper . In the presence of oxidized protein, the T1 values of this proton in reduced azurin depend on the lifetime of the reduced protein . From the T1 data, the electron self-exchange rate constant for azurin was calculated to be 1.4 X 10(4) M-1 X s-1, 4.3 X 10(3) M-1 X s-1, and 6.0 X 10(3) M-1 X s-1 at pH values 4.5, 7.3, and 9, respectively . At pH 7.3, the C-2 proton of His-35 is in slow exchange between the imidazole and imidazolium forms and gives rise to two separate resonances at 9.39 and 8.00 ppm . By using these two resonances, the electron self-exchange rate constants were determined separately for the two species of azurin for which the His-35 residue is in the imidazole or the imidazolium forms; results showed that both species participate in self-exchange of electrons with equal efficiency.

Eur J Clin Microbiol, 1985 Apr, 4(2), 170 - 4
Trafficking of Pseudomonas exotoxin A in mammalian cells; Saelinger CB et al.; Experiments designed to elucidate cellular internalization of Pseudomonas aeruginosa exotoxin A are described . Inhibition of protein synthesis was used as an index of the biological activity of exotoxin A, and a biotinyl-toxin: avidin-gold system to follow its movement on the ultrastructural level . Addition of amantadine, methylamine and dansylcadaverine to cells enhanced the toxicity of exotoxin A at lower concentrations, while protecting cells at higher concentrations . In general, both sensitive and resistant cell lines responded similarly . Exposure of LM or Vero cells to an acidic extracellular pH did not overcome the protection afforded by ammonium chloride against exotoxin A cytotoxicity . This and other data suggest that sensitive and resistant cells may internalize exotoxin A in a similar manner, the toxin entering the cytosol from a prelysosomal acidic vacuole.

Can J Biochem Cell Biol, 1985 Apr, 63(4), 284 - 91
Studies on the primary structure and antigenic determinants of pilin isolated from Pseudomonas aeruginosa K; Sastry PA et al.; The complete amino acid sequence of Pseudomonas aeruginosa K (PAK) pilin was determined using a combination of automated and manual Edman degradation techniques . Suitable peptides were derived from cyanogen bromide, tryptic, chymotryptic, peptic, thermolytic, and citraconylated tryptic cleavages of unmodified or carboxymethylated pilin . The protein, a single polypeptide chain, has N-methylphenylalanine at the NH2-terminus, a total of 144 residues, a molecular weight of 15013, and an equal number of acid and basic amino acids . The NH2-terminal region (residues 1-43) is very hydrophobic with only three charged residues, suggesting a possible role in subunit-subunit interaction . The two half-cystines, residues 129 and 142, are shown to be linked through a disulfide bridge in the native protein . To delineate the antigenic regions of pilin, the protein was cleaved at Arg-30, Arg-53, and Arg-120 to produce peptide fragments cTI (residues 1-30), cTII (residues 31-53), cTIII (residues 54-120), and cTIV (residues 121-144) . cTIII and cTIV were further degraded into several subfragments . The purified peptides were subjected to immunological analysis using direct and competitive enzyme-linked immunosorbent assay procedures . A major antigenic determinant was delineated in a region of the protein encompassing residues 82-101 . Three other epitopes were also identified, but reacted with only minor amounts of antibody in the rabbit polyclonal antiserum.

Zh Mikrobiol Epidemiol Immunobiol, 1985 Apr, (4), 30 - 2
{Polish preparations for preventing and treating infections caused by Pseudomonas aeruginosa}; Schiller B et al.; Three preparations, viz . sheep serum for local application ("Sanoserum"), anti-Pseudomonas sheep immunoglobulin for passive immunization ("Immunoglobulin Pseudomonas") and Pseudomonas vaccine for active immunization ("Pseudovac"), have been obtained at the Central Laboratory of Sera and Vaccines in Warsaw, Poland . The laboratory study and clinical trial of these preparations have been carried out . The preparations have proved to be effective as supplement to the conventional methods for the early diagnosis and treatment of P . aeruginosa infection in burn patients.

Eur J Clin Microbiol, 1985 Apr, 4(2), 224 - 7
Immunotherapeutic potential of monoclonal antibodies against Pseudomonas aeruginosa protein F; Hancock RE et al.; To unambiguously demonstrate the immunotherapeutic potential of outer membrane porin protein F from Pseudomonas aeruginosa, a series of monoclonal antibodies have been isolated and demonstrated to be specific for protein F by Western blotting procedures . The antibodies recognize a surface-exposed antigenic site that is conserved on all Pseudomonas aeruginosa strains tested to date . One of these monoclonal antibodies named MA4-4 resulted in passive protection against subsequent infections by Pseudomonas aeruginosa in two different mouse infection models . In vitro studies using human polymorphonuclear leukocytes suggested that this antibody opsonized Pseudomonas aeruginosa for phagocytosis . The data suggest that immunotherapy based on porin protein F has definite potential for success.

Biochemistry, 1985 Mar 26, 24(7), 1683 - 8
N-terminal analogues of cecropin A: synthesis, antibacterial activity, and conformational properties; Andreu D et al.; Six analogues of the 37-residue antibacterial peptide cecropin A were synthesized by the solid-phase method: cecropin A-(2-37), {Glu2}cecropin A, {Pro4}cecropin A, {Glu6}cecropin A, {Leu6}cecropin A, and {Pro8}cecropin A . Their antibacterial activities against four test organisms were determined and related to conformational changes observed in their CD spectra and were discussed on the basis of a previously proposed amphipathic alpha-helix model . An aromatic residue in position 2 was shown to be important for activity against all tested bacteria . The highly alpha-helical 1-11 region of cecropin A did not appear to play a significant role in its activity against Escherichia coli but was clearly involved in its interaction against Pseudomonas aeruginosa, Bacillus megaterium, and Micrococcus luteus.

J Antibiot (Tokyo), 1985 Mar, 38(3), 346 - 71
Chemical modification of sulfazecin . Synthesis of 4-(substituted methyl)-2-azetidinone-1-sulfonic acid derivatives; Sendai M et al.; In expectation of improving the antibacterial activity of sulfazecin by chemical modification at the 3- and 4-positions, a number of 3-{2-(2-aminothiazol-4-yl)-(Z)-2-(substituted oxyimino)-acetamido}-4-(substituted methyl)-2-azetidinone-1-sulfonic acids were synthesized . Among various 4-substituents explored, the carbamoyloxymethyl group was found to provide a good effect to the antibacterial activity of these 2-azetidinone derivatives . An extensive study of structure-activity relationships led to selecting (3S,4S)-3-{2-(2-aminothiazol-4-yl)-(Z)-2-carboxymethoxyiminoace tamido}-4- carbamoyloxymethyl-2-azetidinone-1-sulfonic acid, AMA-1080 (Ro 17-2301), which has highly potent antibacterial activity against Gram-negative bacteria including Pseudomonas aeruginosa, for further biological and subsequent clinical evaluation.

Am Rev Respir Dis, 1985 Mar, 131(3), 426 - 31
The effects of systemic immunization of pulmonary clearance of Pseudomonas aeruginosa; Dunn MM et al.; Systemic immunization with gram-negative organisms enhances the subsequent pulmonary clearance of these organisms . We studied the early time course of this phenomenon and related it to the time of appearance of polymorphonuclear leukocytes (PMN) and anti-Pseudomonas antibody in bronchoalveolar lavage (BAL) . Mice were immunized intraperitoneally twice, separated by 1 wk, with 10(8) formalin-treated Pseudomonas aeruginosa . Two weeks later, they received an intrabronchial inoculum of 2.9 X 10(6) or 4.6 X 10(7) Pseudomonas organisms . Two, 4, and 6 h later, clearance and total PMN and anti-Pseudomonas antibody in the BAL were assessed . Clearance was enhanced in immunized mice at the lower inoculum . At the higher inoculum, bacteria were growing in lungs of both groups, although they were inhibited in immunized mice . Total PMN in the BAL increased progressively in both groups of mice, but net recruitment was diminished with the high inoculum . There were significant differences in the PMN in the BAL between control and immunized mice with high inoculum . Anti-Pseudomonas IgG first appeared in the BAL at 2 h, anti-Pseudomonas IgM at 6 h . These data suggest that anti-Pseudomonas IgG is an effective early pulmonary opsonin . Further, with high inoculums, immunization may aid pulmonary defenses by diminishing the magnitude of the decrement of PMN in the lung.

Mikrobiologiia, 1985 Mar-Apr, 54(2), 222 - 6
{Role of additional substrates in DDT degradation by cultures of Pseudomonas aeruginosa}; Mal'tseva OV et al.; The activity of enzymes was compared during Pseudomonas aeruginosa 640x growth on compounds activating DDT to a different degree and on acetate which did not stimulate this process . The activity of dehydrogenases generating reduced cofactors necessary for DDT dechlorination was found to be much higher on effective additional substrates than on compounds which either had no effect on DDT degradation or stimulated this process only slightly . The activity of enzymes generating the reduced cofactors was shown to correlate with the extent of DDT degradation by this culture.

Can J Microbiol, 1985 Mar, 31(3), 268 - 75
Immunochemical examination of the Pseudomonas aeruginosa glycocalyx: a monoclonal antibody which recognizes L-guluronic acid residues of alginic acid; Irvin RT et al.; Mice immunized with Formalin-fixed mucoid Pseudomonas aeruginosa cells developed an immune response directed, in part, towards the P . aeruginosa glycocalyx . The polyclonal mouse sera produced good immunofluorescent staining of the P . aeruginosa glycocalyx and cell surface . A library of 250 hybridoma cell lines which produced monoclonal antibodies directed against P . aeruginosa was established . Twelve clones (4.8%) produced antibody which reacted with alginate in an enzyme-linked immunosorbent assay (ELISA) . Clone Ps 53 was chosen for further study, cloned, and an ascites tumor established . Clone Ps 53 was chosen for further study because the antibody produced demonstrated a specificity similar to that of a recently isolated heparin--rat-lung lectin which recognizes alginates of the Homma nontypable P . aeruginosa strains . The Ps 53 clone produced an immunoglobulin M which reacted with P . aeruginosa alginate and produced good immunofluorescent staining of the P . aeruginosa glycocalyx . The Ps 53 monoclonal antibody has an apparent specificity for L-guluronic residues in ELISA . Competitive binding studies with various alginates and monosaccharides suggest that the C6 carboxyl group of uronic acids are recognized by the antibody and that the antigen-binding site is fairly large and may recognize a particular sequence or epitope of alginic acid which is rich in L-guluronic acid . The Ps 53 monoclonal antibody did not react uniformily with all P . aeruginosa alginates but did react with all of the alginates of the Homma nontypable strains tested, suggesting that acetylation or various modifications found in P . aeruginosa alginates may interfere with antibody binding and define specific epitopes . The Ps 53 antibody also reacted with purified outer membrane, indicating that some alginate or L-guluronic acid is intimately associated with outer membrane.

Antimicrob Agents Chemother, 1985 Mar, 27(3), 343 - 9
Efficacy of intermittent versus continuous administration of netilmicin in a two-compartment in vitro model; Blaser J et al.; Several aminoglycoside dosage regimens were studied in a kinetic in vitro model . Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were exposed in serially placed artificial capillary units to netilmicin concentrations that changed based on human two-compartment pharmacokinetics . The same total dose per 24 h was administered as a continuous infusion (3.7 micrograms/ml) or in 1-h infusions given every 24 (24 micrograms/ml) or 8 h (8 micrograms/ml) . The once daily administration showed the best response in terms of either faster killing of E . coli, K . pneumoniae, and S . aureus or greater reduction of the inocula of P . aeruginosa . After 28 h of treatment, however, all regimens reduced the nonpseudomonads by more than 99.99%, whereas all three P . aeruginosa strains regrew to greater than 10(8) CFU/ml due to selection of resistant subpopulations . In contrast to the bactericidal effect of the first dose, no killing occurred after subsequent doses if the ratio of peak drug concentration to MIC was low (less than or equal to 6) . These results support the concept of administering high doses of aminoglycosides once every 24 h.

Zh Mikrobiol Epidemiol Immunobiol, 1985 Mar, (3), 51 - 6
{Effectiveness of a polyvalent corpuscular Pseudomonas aeruginosa vaccine, antibiotics and their combinations in experimental chronic Pseudomonas aeruginosa infection}; Vetkova LG et al.; The data on the development of the experimental model of P . aeruginosa chronic infection in mice, produced by their intraperitoneal inoculation with the infective agent, and on the study of the properties of this model are presented . The model has been used in the experimental study of the preventive action of P . aeruginosa polyvalent corpuscular vaccine . The comparative study, carried out with the use of the proposed model, has been made with a view to evaluating the effectiveness of different methods for the treatment of P . aeruginosa chronic septic infection by means of antibiotics (polymixin B and tobramycin), P . aeruginosa polyvalent corpuscular vaccine and their combination . The combined use of this vaccine with antibiotics (polymixin B or tobramycin) has proved to give the most pronounced curative effect with respect to P . aeruginosa chronic infection.

Infect Immun, 1985 Mar, 47(3), 840 - 2
Decreased delayed-type hypersensitivity and increased protection to Listeria monocytogenes seen in mice infected with mucoid and nonmucoid Pseudomonas aeruginosa; Blackwood LL; Infection of mice with Pseudomonas aeruginosa, washed and unwashed, mucoid and nonmucoid, altered subsequent immunity to Listeria monocytogenes . Mice were protected against lethal doses of L . monocytogenes yet exhibited decreased delayed-type hypersensitivity footpad swelling to sublethal doses . The mucoid coating of mucoid P . aeruginosa, an important pathogen in chronic bronchopulmonary disorders, imparted no additional immunomodulating capabilities to P . aeruginosa.

Infect Immun, 1985 Mar, 47(3), 723 - 9
Quantitation of adherence of mucoid and nonmucoid Pseudomonas aeruginosa to hamster tracheal epithelium; Marcus H et al.; Adherence of mucoid and nonmucoid isolates of Pseudomonas aeruginosa to tracheal epithelium was quantitated by using hamster tracheas mounted in a perfusion chamber . The strains of P . aeruginosa used were clinical isolates from cystic fibrosis patients and a series of laboratory strains . Aseptically excised hamster tracheas were mounted in perfusion chambers and embedded in minimal essential medium containing 1.5% agarose . The tracheas were infected with various numbers of bacteria for various periods, rinsed, homogenized, and plated on Trypticase soy agar . A 4-mm segment from each trachea was prepared for quantitation, and the other segment was prepared for examination by scanning electron microscopy . Adherence increased with time and with increasing concentrations of inoculum . Standard conditions of inoculation were set at an inoculum of 10(7) CFU/ml and a 2-h incubation . Under these conditions, the mucoid organisms adhered to the ciliated epithelium 10- to 100-fold better than did the nonmucoid organisms . Adherence of the mucoid isolates did not appear to be pilus mediated and did not involve hydrophobic interactions . The mucoid P . aeruginosa isolates could be seen adhering to the epithelium in the form of microcolonies embedded in an extracellular matrix which attaches the organisms to the cilia and to each other . The adherence may be involved in the establishment of infection of the lungs of these patients and in the inability to clear the organisms from the lungs . The model will be useful in determining the mechanism of adherence of the bacteria to the ciliated epithelium of the respiratory tract.

Infect Immun, 1985 Mar, 47(3), 659 - 64
Depressing hepatic macrophage complement receptor function causes increased susceptibility to endotoxemia and infection; Loegering DJ et al.; Previous work has demonstrated that in vivo hepatic macrophage complement receptor clearance function is depressed after thermal injury . To determine whether impairment of complement receptor function is important in host defense, the present study evaluated the effect of the depression of complement receptor function in uninjured animals on susceptibility to endotoxin shock and bacterial infection . Hepatic complement receptor clearance function was evaluated by measuring the hepatic uptake of a test dose (2.9 X 10(8)/100 g) of rat erythrocytes coated with anti-erythrocyte immunoglobulin M (EIgM) or EIgG in rats . Depression of hepatic complement receptor function was induced by the injection of EIgG . The hepatic uptake of the test dose of EIgM or EIgG was depressed after the injection of 8.7 X 10(8) EIgG per 100 g and 17.4 X 10(8) EIgG per 100 g but not after the injection of 2.9 X 10(8) EIgG per 100 g . This effect was shown not to be due to a decrease in hepatic blood flow or a depletion of serum C3 and was, therefore, due to a depression in hepatic macrophage complement receptor clearance function . Susceptibility to endotoxin shock was increased with the dose of 8.7 X 10(8) EIgG per 100 g, and susceptibility to infection with Pseudomonas aeruginosa was increased with the dose of 17.4 X 10(8) EIgG per 100 g . Therefore, depression of hepatic macrophage complement receptor clearance function with EIgG is associated with depressed host defense.

Pediatr Infect Dis, 1985 Mar-Apr, 4(2), 172 - 7
Controlled trial of ceftazidime vs . ticarcillin and tobramycin in the treatment of acute respiratory exacerbations in patients with cystic fibrosis; Gold R et al.; A randomized controlled trial was undertaken to compare ceftazidime vs . the combination of ticarcillin and tobramycin in the treatment of acute respiratory exacerbations of mild to moderate severity in patients with cystic fibrosis . The two antibiotic regimens were equally effective in terms of clinical improvement: 16 of 17 in the ceftazidime group and 11 of 13 in the ticarcillin/tobramycin group were judged to be improved by the patients and attending physicians and were observed to show improvement in symptom scores, vital signs, body weight and pulmonary function . Ceftazidime was more effective bacteriologically in reducing colony counts of Pseudomonas aeruginosa in the sputum . Neither regimen affected Pseudomonas cepacia . Resistance to multiple antibiotics developed in six of 12 isolates of nonmucoid P . aeruginosa in patients receiving ticarcillin/tobramycin, which was significantly more than occurred in the ceftazidime group . There was no correlation between clinical and bacteriologic outcomes in either treatment group . No clinically important adverse effects were observed.

J Clin Microbiol, 1985 Mar, 21(3), 332 - 4
Proposed quality control and interpretive criteria for disk diffusion susceptibility testing with enoxacin; Rudrik JT et al.; The standardized disk diffusion test, in which a 10-micrograms enoxacin disk is used, was performed and microbroth dilution MICs were determined to establish individual test control values with Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, and S . aureus ATCC 29213 . In addition, regression analysis correlating inhibitory zone diameter with MICs for approximately 400 gram-negative clinical isolates was performed . Based on linear regression and error rate-bounded analyses, criteria for the category calls of isolates are proposed.

Quad Sclavo Diagn, 1985 Mar, 21(1), 23 - 30
{The Sceptor system: relation of results from antibiograms in diffusion agar to MIC}; Vigano EF et al.; The Sceptor system and the susceptibility of Gram-positive cocci and Gram-negative rods to several antibiotics were presented . The accuracy of methicillin and gentamicin MIC of Staphylococcus aureus was determined . The MIC of methicillin-resistant strain was less than 8 mg/l . Finally the MIC accuracy to 29 Pseudomonas aeruginosa strains was compared with the results obtained by the standard disk diffusion method.

J Hosp Infect, 1985 Mar, 6 Suppl A, 59 - 66
In vitro studies of the killing of clinical isolates by povidone-iodine solutions; Gocke DJ et al.; Two-hundred-and-thirty clinical isolates were surveyed for susceptibility to povidone-iodine (PVP-I) ('Betadine') . Of 95 staphylococcal isolates tested, only 18 (19%) were completely killed by exposure to 10% PVP-I (the usual stock concentration) for 15 s . Seventy-seven staphylococcal isolates (81%) exhibited varying degrees of apparent 'resistance' under these conditions . However, of 39 other Gram-positive isolates and 96 Gram-negative isolates tested (including 20 Pseudomonas aeruginosa and four Ps . cepacia), only one strain of Escherichia coli exhibited significant lack of killing . However, this apparent 'resistance' was completely lost by prolonging the contact time to as little as 30 s in 60% of the isolates, and all isolates were completely killed by 120 s . A paradoxical increase in killing by lower concentrations of PVP-I was observed (maximal killing about 0.1% PVP-I) . A new PVP-I formulation ('SP-Betadine') was completely cidal for all isolates tested after only a 15-s contact time.

J Hosp Infect, 1985 Mar, 6 Suppl A, 127 - 32
Topical burn therapy comparing povidone-iodine ointment or cream plus aserbine, and povidone-iodine cream; de Kock M; A trial comparing three topical agents was carried out in patients with burns . The substances investigated were 10% povidone-iodine (PVP-I) ointment mixed with a proteolytic agent, 5% PVP-I cream alone and in combination with the same proteolytic agent . Differences were observed in healing times and bacteriological cultures . Shorter healing times were observed in burns treated with PVP-I cream . The addition of a proteolytic agent to the cream made no difference to the results . Fewer positive cultures for Staphylococcus aureus and Pseudomonas aeruginosa were obtained in the groups treated with the cream . It was concluded that 5% PVP-I cream is a safe and effective topical agent in burns.

Arch Microbiol, 1985 Mar, 141(2), 170 - 6
Altered control of glutamate dehydrogenases in ornithine utilization mutants of Pseudomonas aeruginosa; Fruh R et al.; Two classes of ornithine-nonutilizing (oru) mutants of Pseudomonas aeruginosa PAO were investigated . Strains carrying the oru-310 mutation were entirely unable to grow on L-ornithine as the only carbon and nitrogen source and were affected in the assimilation of a variety of nitrogen sources (e.g., amino acids, nitrate) . The oru-310 mutation caused changes in the regulation of the catabolic NAD-dependent glutamate dehydrogenase; this enzyme was no longer inducible by glutamate but instead could be induced by ammonia . The oru-310 locus was cotransducible with car-9 and tolA in the 10 min region of the chromosome . An oru-314 mutant was severely handicapped in ornithine medium but could grow when a good carbon source was added; the mutant also showed pleiotropic growth effects related to nitrogen metabolism . The oru-314 mutation affected the regulation of the anabolic NADP-dependent glutamate dehydrogenase, which was no longer repressed by glutamate but showed normal derepression in the presence of ammonia . The oru-314 locus was mapped by transduction near met-9011 at 55 min . Both oru mutants could grow on L-glutamate, L-proline, or L-ornithine amended with 2-oxoglutarate, albeit slowly . We speculate that insufficient 2-oxoglutarate concentrations might account, at least in part, for the Oru- phenotype of the mutants.

J Hosp Infect, 1985 Mar, 6(1), 95 - 7
Outbreak of Pseudomonas aeruginosa following endoscopic retrograde cholangiopancreatography; Earnshaw JJ et al.; In a 12 week period five patients developed gentamicin-resistant Pseudomonas aeruginosa infection after endoscopic retrograde cholangiopancreatography with the same endoscope . The organism was subsequently cultured from the endoscopic apparatus . The cases are discussed and the importance of adequate disinfection of endoscopes is re-iterated.

J Hosp Infect, 1985 Mar, 6(1), 31 - 40
A comparison of sodium hypochlorite and sodium dichloroisocyanurate products; Coates D; A comparison of commercial sodium hypochlorite (NaOCl) and sodium dichloroisocyanurate (NaDCC) products was made . Solutions of NaOCl and NaDCC containing the same levels of available chlorine (av.Cl) exhibited very similar bactericidal activities, despite significant differences in pH . A level of 12.5 ppm av . Cl achieved a greater than 5 log 10 reduction of Staphylococcus aureus in 2 min . A level of 5 ppm av.Cl achieved a greater than 5 log 10 reduction of Pseudomonas aeruginosa in 2 min whilst approximately 100 ppm av.Cl achieved the same reduction in the presence of 1% horse serum, and approximately 200 ppm av.Cl in the presence of 2% horse serum, indicating inactivation levels of around 95 and 97.5% respectively . Tablets of NaDCC were stable but solutions were unstable and decomposed much faster than NaOCl solutions of the same strength . Batch-to-batch variability of different NaOCl and NaDCC products was investigated; whilst NaDCC products always contained the minimum level of av.Cl specified, concentrated NaOCl products sometimes did not due to inherent instability.

Biochem Biophys Res Commun, 1985 Feb 28, 127(1), 198 - 204
Effect of Pseudomonas aeruginosa exotoxin-A on the synthesis and secretion of proteins in isolated rat pancreatic acini; Geokas MC et al.; Exposure of isolated rat dispersed pancreatic acini to increasing concentrations (10 to 1000 ng/ml) of purified exotoxin-A from Pseudomonas aeruginosa resulted in a progressive inhibition of 3H-leucine incorporation into "cellular" (those remaining in the cells) and "secretory" (those released into the medium) proteins . With each concentration of exotoxin-A, magnitude of reduction was found to be greater for the "secretory" proteins than that observed for the "cellular" proteins . Thus, in the presence of 250 ng/ml of exotoxin-A, a dose that produced maximal inhibition in protein synthesis, 3H-leucine incorporation into "cellular" and "secretory" proteins was found to be decreased by about 19 and 50%, respectively, when compared with the corresponding basal controls . Release of trypsinogen, chymotrypsinogen and amylase from the isolated pancreatic acini was also inhibited by high doses of exotoxin-A . However, whereas the exotoxin concentration of 1000 ng/ml, caused a near complete inhibition of chymotrypsinogen release, trypsinogen and amylase secretion were decreased by 40 and 50%, respectively . It is concluded that in isolated pancreatic acini, exotoxin-A inhibits the synthesis and secretion of proteins.

J Biol Chem, 1985 Feb 25, 260(4), 2432 - 6
Primary structure of the reactive site of human C1-inhibitor; Salvesen GS et al.; Human C1-inhibitor (C1-Inh) forms an equimolar complex with complement proteinase C1s that is resistant to dissociation by sodium dodecyl sulfate . The formation of this stable complex results in the cleavage of a peptide bond near the carboxyl terminus of the inhibitor and, whereas the bulk of C1-Inh remains covalently bound to the light chain of C1s, the postcomplex inhibitor peptide can be isolated under denaturing conditions . We have sequenced the amino-terminal region of this peptide and deduced that it represents the carboxyl-terminal side of the reactive site of C1-Inh . Limited proteolysis of C1-Inh by Crotalus atrox protease results in an active derivative lacking an amino-terminal peptide of 36 residues . Further proteolysis of this derivative with Pseudomonas aeruginosa elastase inactivates the inhibitor and a peptide is released . The amino-terminal sequence of this peptide overlaps with that of the postcomplex peptide and indicates that the residue imparting primary specificity to the inhibitor is arginine.

JAMA, 1985 Feb 22, 253(8), 1156 - 9
Pseudomonas dermatitis associated with a swimming pool; Thomas P et al.; One hundred forty-seven (66%) of 224 scouts and chaperons were interviewed after a weekend visit to a dude ranch in upstate New York . One hundred seventeen (80%) complained of papular rashes or eye and ear inflammation . Onset of illness occurred within 24 to 48 hours of arrival at the ranch . After controlling for participation in other available activities, only swimming was found to be associated with illness . Pseudomonas aeruginosa serotype 0 11 grew from a culture of pool water and from 17 cultures of skin, eye, and ear lesions in visitors to the ranch . Follow-up was obtained for 76 of the affected persons for whom initial information was available . Mean duration of illness was 14.5 days (range, one to 40+ days) . The recurrence rate was 24%.

Biochem J, 1985 Feb 15, 226(1), 37 - 42
Comparison of different techniques for estimating rates of protein synthesis in vivo in healthy and bacteraemic rats; Pomposelli JJ et al.; Previous studies have reported that use of a flooding dose of radiolabelled amino acid is a more precise technique than the constant infusion of tracer quantities for determining rates of protein synthesis in rapidly turning-over tissues in the rat . However, there has been little direct investigation comparing different methods under comparable conditions . Initially, 12 healthy male Sprague-Dawley rats, weighing approx . 100 g, were randomized to receive either a bolus intravenous injection of 100 mumol of L-leucine (containing 30 microCi of {1-14C}leucine)/100 g body wt., or a continuous 2 h tracer infusion of {14C}leucine . In the second phase of the experiment, 12 additional rats were intravenously injected with 1 X 10(8) colony-forming units of Pseudomonas aeruginosa and 16 h later randomized to receive one of two infusions described above . Total protein synthesis as well as fractional synthesis rates were determined in liver, rectus muscle and whole body . Synthesis rates measured in liver, muscle and whole body were significantly higher in bacteraemic rats than in healthy rats . The flooding-dose methodology gave significantly higher estimates of protein synthesis in the liver, skeletal muscle and whole body than did the continuous-infusion method using direct measurement of the acid-soluble fraction from the respective tissue . Indirect estimates of whole-body protein synthesis based on plasma enrichments and stochastic modelling gave the lowest values.

Can Med Assoc J, 1985 Feb 15, 132(4), 381 - 4
Invasive external otitis: review of 12 cases; Salit IE et al.; Invasive external otitis is an infection caused by Pseudomonas aeruginosa that often occurs in elderly people with diabetes . Twelve cases that illustrate the problems associated with the clinical recognition and successful outcome of the condition were reviewed . The patients' average age was 62.5 years, and they had been ill for an average of 1.8 months before admission to hospital . Predisposing factors included diabetes, swimming in a warm climate and the use of a hearing aid . Radionuclide bone scanning and surgical exploration revealed pathognomonic findings . Initial therapy was often suboptimal: one or more relapses occurred in seven of the patients . All of the patients were cured without relapse after a minimum of 4 weeks of therapy with tobramycin plus an anti-Pseudomonas penicillin . The average duration of the illness was 3.9 months . The outcome in invasive external otitis should be excellent if the condition is diagnosed early and appropriate therapy is instituted.

Aust Vet J, 1985 Feb, 62(2), 55 - 7
Immunisation of sheep against experimental Pseudomonas aeruginosa dermatitis and fleece-rot associated body strike; Burrell DH; Sheep immunised with an experimental Pseudomonas aeruginosa vaccine and unvaccinated control sheep were challenged by induction of experimental dermatitis with the homologous strain . All of 6 control sheep developed ulcerative dermatitis, and 2 of the 6 challenge sites were struck by larvae of Lucilia cuprina . Neither severe dermatitis nor strike occurred in 6 vaccinated sheep . These results were confirmed in an experimental challenge using 3 different serotypes of P . aeruginosa on each of 3 vaccinated and control sheep, although fly-strikes did not occur . In a field trial of the same vaccine, none of 26 vaccinated sheep developed severe exudative, fleece-rot lesions nor were any fly-struck, whereas 61 of 115 control sheep developed severe, exudative, fleece-rot lesions, 21 of these becoming struck by L . cuprina . The isolates of P . aeruginosa recovered from the field challenge experiment were a different serotype to that used in the vaccine.

Chemioterapia, 1985 Feb, 4(1), 102 - 9
The emergence of resistance to beta-lactam antibiotics during treatment of Pseudomonas aeruginosa lower respiratory tract infections: is combination therapy the solution?
Nichols L, Maki DG.
Treatment of Pseudomonas aeruginosa lower respiratory tract infections with beta-lactam antibiotics alone (beta-lactam monotherapy) has been thought to result in a high incidence of therapeutic failure due to the emergence of multiply-resistant strains on the basis of induction of a chromosomal beta-lactamase . Review of published experience in patients without granulocytopenia or cystic fibrosis suggests that favorable clinical responses can be obtained in 80-90% of cases, and bacteriological cures in 45-55%, using any of the newer beta-lactam antipseudomonal agents alone (data from cefsulodin, cefoperazone, azlocillin and piperacillin) . Resistance develops in 30-40% of the infecting organisms, and is associated with treatment failure in 10-20% of cases (data from cefsulodin, ticarcillin and carbenicillin) . Cross-resistance to other beta-lactams and to aminoglycosides can occur but seems unlikely to be on the basis of induction of a chromosomal beta-lactamase (data from cefsulodin) . The addition of an aminoglycoside antibiotic (combination therapy) has been recommended to prevent these outcomes . Retrospective comparison with results obtained using combination therapy in patients without granulocytopenia or cystic fibrosis suggests that the addition of an aminoglycoside cannot be expected to prevent either the development of resistance or therapeutic failure (which are frequently unassociated) . Treating every patient with a Pseudomonas aeruginosa lower respiratory tract infection with combination therapy will expose all of them to the toxicity of an aminoglycoside but will rarely repay this risk with the prevention of a multiply resistant strain or the salvage of a patient destined to fail beta-lactam monotherapy.

J Antimicrob Chemother, 1985 Feb, 15(2), 233 - 8
Primaxin in the treatment of acute bacterial pneumonia in adults; Gebhart RJ et al.; Imipenem (N-Formimidoyl thienamycin) (MK-0787) is a new beta-lactam carbapenem antibiotic . When it is combined with the renal dipeptidase inhibitor cilastatin (MK-0791) the combination is known as primaxin . In this study 28 adult patients (24 males and 4 females) with acute bacterial pneumonia were treated with primaxin . Twenty-one patients were evaluable and 20 (95%) were clinically cured of their pneumonia . Bacteriological cures were demonstrated in 84% of the cases . One patient with a susceptible Pseudomonas aeruginosa failed . Major complications or toxic reactions included antibiotic associated diarrhoea in one patient; hypotension in one patient; increased grand mal seizures in one patient and elevated liver function studies in one patient . Results of this study suggest that primaxin will be useful in the treatment of a variety of serious Gram-positive and Gram-negative pneumonias . The true incidence of possible toxic reactions with this drug is not known at this time and awaits further experience.

Arch Ophthalmol, 1985 Feb, 103(2), 270 - 4
Polymorphonuclear leukocyte kinetics in experimentally induced keratitis; Chusid MJ et al.; The movement of polymorphonuclear leukocytes (PMNLs) into inflamed corneas was studied using a quantitative technique to measure PMNL chemotaxis in vivo . Our studies suggested that, in this model, most PMNLs enter the cornea through limbal vessels . A variety of bacterial agents, including viable bacteria, killed bacteria, culture filtrates, and endotoxin, were found to induce a significant corneal inflammatory response . Of the agents tested, viable Pseudomonas aeruginosa produced greatest inflammation . Host factors (serum, PMNLs) also induced movement of PMNLs into corneas, but only after preincubation with activating agents . Normal serum, resting PMNLs, and PMNL lysates derived from resting cells did not promote PMNL corneal ingress . These studies provide further insight into the movement of PMNLs into the inflamed cornea and information that may be of use in developing techniques to inhibit the corneal inflammatory response.

J Bone Joint Surg Am, 1985 Feb, 67(2), 175 - 85
Local muscle flaps in the treatment of chronic osteomyelitis; Fitzgerald RH Jr et al.; When large soft-tissue and osseous defects remain after debridement of a chronic osteomyelitic lesion, application of a local muscle flap can be an effective way to achieve wound closure . Utilizing this surgical technique and specific antimicrobial therapy for the causal microorganisms, the infectious process was eradicated in thirty-nine of forty-two patients with osteomyelitis who were followed for at least two years after treatment . The osteomyelitic process was post-traumatic in origin--that is, a complication of a fracture or its treatment--in twenty-eight patients, the result of soft-tissue trauma without a fracture in eight, a complication of elective surgery in three, and the result of hematogenous seeding in three patients . Nine of the forty-two patients had an infected non-union . The infectious process involved the tibia in 62 per cent of the patients . Pseudomonas aeruginosa was the most frequently isolated causal organism . A soleus or gastrocnemius muscle flap was most frequently utilized to achieve closure . In five patients, a combination of two muscle flaps was utilized . Although this technique successfully eradicated the infectious process in 93 per cent of the patients, twenty-two patients required additional surgical treatment . Six required such treatment for a persistent non-union and two, for weakened diaphyseal bone after eradication of the septic process . A cancellous bone-grafting procedure was performed in all eight patients after the muscle flap had healed, and union was achieved in six of them . One patient eventually requested an amputation for a persistent non-union, and the remaining patient had a fibular synostosis performed for a persistent tibial non-union . A local muscle flap can be used in patients with a large defect of soft tissue and bone after debridement of an osteomyelitic lesion if the flap can be elevated and transposed into the defect without compromising its vascular supply . Although they are not applicable to the treatment of all patients with osteomyelitis, local muscle flaps can be extremely useful in the treatment of this lesion . When combined with thorough debridement and specific antimicrobial therapy, it has become a successful technique in the management of chronic osteomyelitis.

Antibiot Med Biotekhnol, 1985 Feb, 30(2), 83 - 6
{Tetracycline resistance controlled by plasmids of Pseudomonas aeruginosa with a wide spectrum of bacterial hosts}; Kozlova EV et al.; PBS222 and pBS223 plasmids with a wide spectrum of bacterial hosts detected in strains of P . aeruginosa control resistance of the cells of P . aeruginosa ML4262 (PAO) and E . coli C600 to 300 and 200 micrograms/ml of oxytetracycline respectively increasing 15 and 20 times their resistance to the antibiotics . The constant of the antibiotic elimination from the cells of P . aeruginosa ML4262 containing pBS223 plasmid is 3.5 times higher than the entry constant, while the constants of the antibiotic entry and elimination in the cells containing pBS222 plasmid are almost the same . Accumulation of tetracycline by the cells containing pBS223 plasmid decreases 2.8 times and that by the cells containing pBS222 plasmid decreases 1.7 times . The determinants of tetracycline resistance in pBS222 and pBS223 plasmids may be referred to the class TetC.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1985 Feb, 259(1), 104 - 17
Influence of different immunoglobulin G preparations on phagocytosis of Pseudomonas aeruginosa by polymorphonuclear granulocytes; Trautmann M et al.; Commercially available immunoglobulin products suitable for intravenous application in humans are made by enzymatic or chemical modification of the IgG molecule . In order to examine, to which extent in vitro biologic functions of the IgG molecule are preserved in such preparations, specific antipseudomonal IgG from the rabbit was modified according to some of these procedures . The opsonizing activity of the different IgG preparations was evaluated in an in vitro system measuring the phagocytosis of Pseudomonas aeruginosa by rabbit granulocytes . The results demonstrated that the product Fab/Fc, which is made by papain or plasmin degradation of the IgG molecule, was still able to enhance phagocytosis but not to activate complement . The smaller papain- or plasmin-derived fragments Fab and Fc had no opsonizing activity . The pepsin-derived product F(ab')2 which possesses a divalent antigen binding site but lacks the Fc part, only enhanced phagocytosis when complement concentrations of more than 20% were present in the phagocytic system . Since the F(ab')2 fragment is not able to interact with Fc receptors or to activate complement via the classical pathway, the phagocytosis-enhancing activity of this molecule must be attributed to alternative complement pathway activation . In contrast to the enzymatically derived IgG preparations, a newly developed S-sulphonated IgG product was as efficient as unmodified IgG both in Fc- and complement-mediated opsonization.

Zh Mikrobiol Epidemiol Immunobiol, 1985 Feb, (2), 27 - 32
{Pseudomonas aeruginosa toxoid}; Ianishevskaia MN; P . aeruginosa adsorbed toxoid has been obtained . The stabilization of exotoxins and the content of proteases, hemolysin, lecithinase in their structure have been found to enhance the immunogenic potency of preparations which protect test animals from death caused by the experimental injections of toxins, homologous and heterologous to bacterial strains of different O-serogroups, into these animals . Antibodies neutralizing the lethal action of P . aeruginosa exotoxin have been detected in the blood sera of immunized animals.

Zh Mikrobiol Epidemiol Immunobiol, 1985 Feb, (2), 11 - 4
{Characteristics of hospital strains of Pseudomonas aeruginosa}; Iskhakova KhI; A total of 745 P . aeruginosa strains from patients with purulent inflammatory processes, 216 strains from the environment of a surgical hospital and 35 strains from carriers were studied with respect to 30 cultural and biochemical signs of P . aeruginosa . 19.8% of the strains were found to form no pigment, and in 14.8% of the strains delayed pigment formation was observed (on days 3-10) . The most stable signs were motility (99.6%), growth in Simmons citrate agar (97.6%), growth at 42 degrees C (97.4%), arginine decarboxylase activity (96.8%) . In 77.0% of the strains glucose assimilation in Hiss liquid medium, in 85.6% glucose oxidation in the OF test, in 90.8% the formation of urease and in 93.2% the formation of gelatinase were observed . Among the strains isolated from the environment, P . aeruginosa variants, atypical with respect to their main differentiating signs, were isolated significantly more frequently.

Chemioterapia, 1985 Feb, 4(1), 95 - 101
Emergence of resistance to beta-lactam antibiotics in Pseudomonas aeruginosa during treatment with new beta-lactams; Lerner SA et al.; In 12 patients treated with cefsulodin for Pseudomonas aeruginosa infections, resistance to cefsulodin developed in the infecting strains of two patients who failed to improve clinically . In both cases, cross-resistance also appeared for a broad spectrum of new antipseudomonal beta-lactams, except imipenem . The resistant isolate from one patient had a new constitutive beta-lactamase for cephalothin which also had modest activity for cefsulodin, ceftazidime, and carbenicillin . Furthermore, all of the non-hydrolyzed beta-lactams appeared to be bound by a beta-lactamase in this isolate . The origin and role in beta-lactam resistance of the observed beta-lactamase activity are obscure . The resistant isolate from the other patient had no demonstrable beta-lactamase activity that could account for the beta-lactam resistance . In five patients treated with imipenem for P . aeruginosa infections, resistance to imipenem developed in the strains of two patients who failed to improve clinically . The strain from one patient was already resistant to all other antipseudomonal beta-lactams before imipenem therapy . The initial strain from the other patient was broadly susceptible, and it developed resistance only to imipenem . Prior to imipenem therapy, another patient, who had P . aeruginosa endocarditis, had isolates from blood with three different susceptibility patterns: susceptible to all antipseudomonal beta-lactams, resistant to all but imipenem, and resistant to imipenem alone . There was no demonstrable beta-lactamase activity to account for imipenem resistance in any of the isolates in these patients . None of the resistant P . aeruginosa isolates had a change in penicillin-binding proteins from those of their susceptible counterparts that might explain the development of resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemioterapia, 1985 Feb, 4(1), 36 - 42
beta-Lactamases of Pseudomonas aeruginosa and susceptibility against beta-lactam antibiotics; Thabaut A et al.; A total of 4093 non-replicate Pseudomonas aeruginosa isolates supplied by 10 French hospitals from September 1981 to August 1983 was examined for susceptibility to ticarcillin (TIC) and to 11 other beta-lactam antibiotics . Overall incidence of TIC-resistance was low (20.9%) but variable between hospital, unit and culture site and primarily mediated by a constitutive beta-lactamase as observed by iodometric detection (66.3%) . As suggested by analytical isoelectrofocusing on gel, PSE-1 (CARB-2) and OXA types were predominant but new types appeared . The comparative in vitro activities of 12 antipseudomonal beta-lactams appreciated by microtiter MICs with an inoculum of 10(5) CFU were established according to phenotype: TIC-susceptible, TIC-R with a constitutive beta-lactamase (PSE-1, OXA-1, OXA-2, OXA-3, PSE-2 and a new type, TEM-1 and TEM-2 and derepressed cephalosporinase) or without detectable activity . Different patterns of resistance were demonstrated, but imipenem, ceftazidime and aztreonam were the most active antibacterial agents.

Chemioterapia, 1985 Feb, 4(1), 28 - 35
Cephalosporin resistance in Pseudomonas aeruginosa, with special reference to the proposed trapping of antibiotics by beta-lactamase; Livermore DM et al.; Resistance of Pseudomonas aeruginosa strains to newer cephalosporins is often associated with stable derepression of synthesis of the chromosomal beta-lactamase . Similar resistance is developed by enzyme inducible (i.e . normal) strains in response to beta-lactamase inducers . By comparing the responses of otherwise isogenic P . aeruginosa beta-lactamase inducibility mutants to antipseudomonal cephalosporins alone or in combination with potent beta-lactamase inducers we confirmed that resistance to cefotaxime, ceftriaxone, cefoperazone, and ceftazidime and latamoxef was caused by beta-lactamase action . The low-level resistance to carbenicillin and cefsulodin which was exhibited by some fully beta-lactamase derepressed strains was not confirmed to be beta-lactamase determined and may have reflected concurrent target or permeability changes . The mechanism whereby the enzyme protected the cell against cefotaxime and ceftriaxone was also investigated . These agents are reportedly stable to the enzyme and some workers have suggested that resistance entails their being trapped rather than hydrolysed . However, the use of a novel model of cellular beta-lactamase function indicated that a hydrolytic resistance mechanism remained likely.

Eur J Biochem, 1985 Feb 1, 146(3), 693 - 7
Monoclonal antibodies against species-specific cephalosporinase of Pseudomonas aeruginosa; Murakami K et al.; Ten hybridomas which produced monoclonal antibodies against species-specific cephalosporinase of Pseudomonas aeruginosa were constructed by somatic cell fusion of SP-2/0 myeloma cells with spleen cells from hyperimmunized BALB/c mice and intraperitoneally injected into mice . Monoclonal antibodies were partially purified from ascites fluids . All ten antibodies thus prepared were IgG immunoglobulins . In a solid-phase immunoassay the antibodies gave positive reactions which could be prevented by the presence of free cephalosporinase . When the antibodies were precipitated with anti-(mouse IgG), the cephalosporinase activity was co-precipitated . Also, these antibodies were co-eluted with cephalosporinase activity in gel filtration . Nine of the monoclonal antibody preparations elevated the cephalosporinase activity by about 6-40% and only one inhibited it by about 50% . All the monoclonal antibodies were highly specific to P . aeruginosa cephalosporinase and showed no cross-reaction with nine cephalosporinases and four penicillinases of other gram-negative bacteria.

J Med Microbiol, 1985 Feb, 19(1), 45 - 53
PSE-4 beta lactamase: a serotype-specific enzyme in Pseudomonas aeruginosa; Livermore DM et al.; PSE-4 enzyme is the most common plasmidic beta lactamase in Pseudomonas aeruginosa but its production is invariably non-transferable by conjugation . Of 20 PSE-4+ isolates from 10 separate sources, 16 were serotype O:16 and two belonged to the related O:2(b) serotype . One of the two remaining organisms was not O-typable and the other was agglutinated by several unrelated antisera . Examination of additional O:16 strains confirmed the unusual frequency of PSE-4 enzyme in this serotype . None of the PSE-4+ strains was able to transfer carbenicillin resistance in mating experiments and none contained extrachromosomal DNA . Two explanations of the relationship between enzyme production and O antigenicity are proposed . PSE-4 production may be transmissible, perhaps by transduction, between strains of O:16 or related serotypes, or PSE-4+ P . aeruginosa may represent a disseminated subtype . A third hypothesis, that the PSE-4 coding element carried serotype determinants, was discounted . PSE-4+ and PSE-4- P . aeruginosa strains of O:16 and related serotypes were found to represent a definite cluster by their phage-susceptibility pattern and pyocin type (type 1) . The only characters linked to PSE-4 production were resistance to spectinomycin, streptomycin and sulphonamide and the genes responsible for these characters seemed to occur on the PSE-4 coding element.

J Infect Dis, 1985 Feb, 151(2), 209 - 16
Selective survival in pentazocine and tripelennamine of Pseudomonas aeruginosa serotype O11 from drug addicts; Botsford KB et al.; The growth of Pseudomonas aeruginosa, particularly serotype O11, in pentazocine and tripelennamine ("T's and Blues") was evaluated as a possible explanation for the association of deep-seated infection with this organism and abuse of these drugs . The mean reduction of growth caused by the drugs was 1,000-fold greater for 49 Pseudomonas strains from normal subjects than for 32 strains from drug addicts (4.2 vs . 1.3 logs of reduction at 2 hr, P less than .0005) . A common phenotypic subset of the serotype O11 strains from drug addicts was especially resistant to the inhibitory effects . Twelve strains of Staphylococcus aureus (a frequent cause of infection in heroin, but not in pentazocine and tripelennamine, addicts) were completely inhibited by the drug combination . Dose-response curves (derived from the results of using the tablets as well as pure powders) showed that tripelennamine was responsible for the inhibitory activity, which was partially antagonized by pentazocine . We conclude that an ability of some P . aeruginosa serotype O11 strains, but not S . aureus, to survive in pentazocine and tripelennamine may explain in part a shift from S . aureus to P . aeruginosa as common pathogens of drug addicts in areas where abuse of this combination of drugs has increased.

J Infect Dis, 1985 Feb, 151(2), 203 - 8
Outbreak of endocarditis caused by Pseudomonas aeruginosa serotype O11 among pentazocine and tripelennamine abusers in Chicago; Shekar R et al.; At Cook County Hospital (Chicago), before 1977, the incidence of endocarditis caused by Pseudomonas aeruginosa was one or two cases per year . The frequency of P . aeruginosa as an etiologic agent of endocarditis among drug abusers increased steadily from five (23%) of 22 patients in 1977 to 15 (68%) of 22 in 1980 . P . aeruginosa serotype O11 accounted for 34 (76%) of 42 of the strains serotyped . The total increase in incidence of P . aeruginosa endocarditis that we observed can be attributed to disease caused by serotype O11 . We serotyped 152 strains of P . aeruginosa obtained from hospital inpatients without endocarditis . Serotype O11 was the most frequently isolated type, accounting for 27% of the total . Incidence of serotype O11 in drug addicts with endocarditis is significantly higher than the incidence in patients with nonendocarditis infections (chi 2 = 32.89; P less than .001) . There was a high degree of correlation between pentazocine and tripelennamine ("T's and Blues") abuse and endocarditis caused by P . aeruginosa (chi 2 = 36.71; P less than .001).

Infect Immun, 1985 Feb, 47(2), 555 - 60
In vitro evidence that human airway lysozyme is cleaved and inactivated by Pseudomonas aeruginosa elastase and not by human leukocyte elastase; Jacquot J et al.; The in vitro effects of Pseudomonas aeruginosa elastase (P . aeruginosa E) and of human leukocyte elastase on human airway lysozyme (HAL) were investigated . P . aeruginosa E inactivated and cleaved HAL, whereas human leukocyte elastase had no effect . Total inactivation of HAL by P . aeruginosa E was observed after 120 min of incubation at 37 degrees C, for an elastase-to-lysozyme molar ratio of 1:5 . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reaction mixtures containing HAL and P . aeruginosa E in an elastase-to-lysozyme molar ratio of 1:10 showed a progressive disappearance of the HAL band upon increasing the incubation time with P . aeruginosa E . Gel filtration chromatography indicated that HAL was cleaved into at least three peptide fragments . The cleavage of HAL by P . aeruginosa E was accompanied by parallel losses of its bacteriolytic activity and its immunoreactive property.

Am J Infect Control, 1985 Feb, 13(1), 16 - 20
Effect of an expanded physical facility on nosocomial infections in a neonatal intensive care unit; Larson E et al.; Fifty-two months' data were reviewed to assess the effect of a threefold increase in space per infant in a neonatal intensive care unit on rates of nosocomial infections (NIs) and colonization with Staphylococcus aureus (39 months in a crowded 18-bed unit and 13 months in a spacious 32-bed unit) . Mean length of stay, survival rates, mean birth weights, and other parameters indicated that infant populations in the old and new units were similar . NI rates were not significantly different in the old and new units (11.7% and 9.6%, respectively; p = 0.17) nor were rates of colonization of anterior nares with S . aureus (11.7% and 10.7%; p = 0.5) . NI rates, but not S . aureus colonization rates, were significantly higher during months of high patient turnover (p less than 0.01) . Sites of infection were similar in the old and new units . There was, however, a significant change in bacterial species causing NI . Klebsiella pneumoniae and Pseudomonas aeruginosa caused 20.4% of NIs in the old unit, but only 2.1% in the new unit (p less than 0.001) and NIs caused by S . epidermidis increased from 4.7% to 14.9% (p = 0.02) in the new unit . There was also a marked decrease in the numbers of clusters of NI occurring in the new unit, indicating that cross-infections between infants were probably minimized.

J Appl Physiol, 1985 Feb, 58(2), 326 - 38
Alteration of surfactant function due to protein leakage: special interaction with fibrin monomer; Seeger W et al.; In isolated rabbit lungs standardized amounts of edema were induced . Stimulation with the Ca ionophore A23187, leukotriene C4, Pseudomonas aeruginosa cytotoxin and human serum (activated complement) all resulted in protein leakage into the alveolar space with no change in the total phospholipid content . The pressure-volume characteristics of the lungs and the characteristics of the lavage surfactant (Wilhelmy balance) were markedly altered, correlating to the lavage protein content . The surfactant alterations were reproduced by addition of perfusion fluid protein to control surfactant in vitro . All changes were far less expressed or even missing in isolated lungs developing the same amount of edema due to omittance of proteins from the perfusion liquid . Different proteins added to control surfactant in the Wilhelmy balance showed a marked rank order of potency in interfering with surfactant function: immunoglobulins G and M and elastin less than albumin less than fibrinogen less than fibrin monomers . The fibrin monomer effect was reproduced by addition of thrombin to a surfactant fibrinogen mixture and was partly reversed by subsequent incubation with plasmin . In conclusion, high-permeability edema induced by different means results in alterations of lung mechanics and surface activity of lavaged surfactant, presumably due to protein surfactant interaction . Among different proteins, fibrin monomers are especially effective in interfering with surfactant function.

J Infect Dis, 1985 Feb, 151(2), 291 - 4
Ciprofloxacin as therapy for experimental osteomyelitis caused by Pseudomonas aeruginosa; Norden CW et al.; Ciprofloxacin, a new carboxyquinoline antimicrobial agent, was compared with tobramycin in the treatment of chronic osteomyelitis due to Pseudomonas aeruginosa in rabbits . Treatment with tobramycin for four weeks was ineffective (94% had positive bone cultures) . In contrast, ciprofloxacin administered for four weeks sterilized the bones of all but one (94%) of 18 treated rabbits . Treatment with ciprofloxacin for two weeks was less effective than treatment for four weeks but was more effective than either treatment with tobramycin or no therapy . Two of 10 isolates from rabbits treated with ciprofloxacin for two weeks were susceptible to MICs of ciprofloxacin that were 16- and fourfold greater than the MIC for the parent strain; the other eight isolates remained sensitive to ciprofloxacin with MICs equivalent to that of the parent strain.

Arch Biochem Biophys, 1985 Feb 1, 236(2), 714 - 9
A rapid-scan spectrometric and stopped-flow study of compound I and compound II of Pseudomonas cytochrome c peroxidase; Ronnberg M et al.; A quantitative yield of half-reduced (ferrous-ferric) cytochrome c peroxidase from Pseudomonas aeruginosa has been obtained by using either ascorbate or NADH as reductant of the resting (ferric-ferric) enzyme along with phenazine methosulfate as mediator . The formation of Compounds I and II from the half-reduced enzyme and hydrogen peroxide has been studied at 25 degrees C using rapid-scan spectrometry and stopped-flow measurements . The spectra of Compound I in the Soret and visible regions were recorded within 5 ms after mixing the half-reduced enzyme with H2O2 . The spectrum of the primary compound at the Soret region had a maximum at 414 nm, and in the visible region at 528 and 556 nm . The spectrum of Compound I showed no bands in the 650-nm region, excluding the possibility of a pi-cation radical being part of the catalytic mechanism . Compound I was stable for at least 12 s when no reducing equivalents were present . In the presence of reduced azurin, half-reduced enzyme reacted with H2O2 to form Compound II within 50 ms . The spectrum of Compound II had a Soret maximum at 411 nm . In the visible region the Compound II spectrum was close to that of the totally oxidized, resting enzyme form . In the presence of excess azurin, Compound II was converted rapidly to the half-reduced enzyme form . The kinetics of Compound I formation was also followed with peracetic acid, ethylhydroperoxide, and m-chloroperbenzoic acid as electron acceptors . The rate constants of these reactions are diminished compared to that of hydrogen peroxide, indicating a closed structure for the heme pocket of the enzyme.

Acta Pathol Microbiol Immunol Scand {B}, 1985 Feb, 93(1), 7 - 13
Polyagglutinability due to loss of O-antigenic determinants in Pseudomonas aeruginosa strains isolated from cystic fibrosis patients; Ojeniyi B et al.; O-polyagglutinable P . aeruginosa are prevalent among chronically infected cystic fibrosis patients . In the present work, one O-group 3, one O-group 9 and one polyagglutinable 0-3/9 strain were analysed by use of both corresponding group specific antisera against the O-antigen and polyspecific antisera against all extractable antigens of the 3 strains . Quantitative immunoelectrophoresis and classical tube-agglutination methods were employed in the analysis . The results showed that the polyagglutinable strain contained 0.1% and the 0-9 strain 1%, respectively, of the O-antigen-containing LPS present in the 0-3 strain . It is discussed whether these differences represent a gradual antigenic adjustment to the defence mechanisms of the chronically infected patients.

Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1985 Feb, 18(1), 37 - 43
{Serotype distribution of Pseudomonas aeruginosa . Comparative studies of nosocomial and community strains}; Chao HP et al.; A total of 202 strains of Pseudomonas aeruginosa were collected from December 1980 to September 1982 at National Taiwan University Hospital . Of the 202 strains, 102 were nosocomial strains and the other 100 were community strains . The distribution of O antigen group were as follow: E, 34.2%; B, 17.3%; G, 10.9%; F, 9.9%, I, 7.9%; L, 7.4%; others, 12.4% . The antisera used were produced by Toshiba Kagaku Kogyo Co., Japan . The relationship between antibiotic susceptibility pattern and O antigen group were that group-I was the most susceptible group and group-L was the most resistant group . With the O antigen grouping and antibiotic susceptibility pattern, we tried to differentiate the nosocomial strains from the community strains . No obvious difference could be drawn.

Eur J Biochem, 1985 Jan 2, 146(1), 35 - 42
Mechanisms of activation and secretion of a cell-associated precursor of an exocellular protease of Pseudomonas aeruginosa 34362A; Fecycz IT et al.; An inactive precursor to the active exocellular protease 1 of Pseudomonas aeruginosa is cell-associated and located primarily in the periplasmic space . We have studied factors that bring about activation of the precursor in vitro in order to shed some light on the process of its activation and secretion in vivo . A variety of diverse procedures were shown to effect irreversible activation . Several mild non-enzymatic procedures were effective, such as dialysis of an ammonium sulfate precipitate against neutral buffers, gel filtration (Sephadex G-100), and ion-exchange chromatography (DEAE-cellulose) . Activation also resulted following treatment with anionic detergents (sodium dodecyl sulfate, N-lauroyl sarcosine) and deoxycholate . Limited exposure to any of several proteases with different specificities also resulted in activation . The kinetics of detergent-catalyzed activation reveals a long lag followed by rapid activation, suggesting at least a two-stage process . The precursor and the mature protease 1 have indistinguishable molecular masses (33 kDa), as measured by sodium dodecyl sulfate/polyacrylamide gel electrophoresis of these proteins purified by immunoabsorbance chromatography under denaturing conditions . Further, both precursor and protease have identical N-terminal alanine . Our results suggest that it is improbable that activation is the result of proteolytic processing of the precursor itself, but rather that it may involve the removal of a non-covalently associated inhibitor molecule . Hydrophobic interaction chromatography on octyl-Sepharose revealed that activation was accompanied by a significant change in the hydrophobicity, pointing to a significant change in the conformation of the precursor and the mature protease . A mutant has been studied which accumulates activatable precursor in the periplasm but releases no active enzyme into the culture medium, supporting the hypothesis that secretion through the inner and outer membranes proceed by different mechanisms . Comparison of outer membranes of protease-secreting strains (34362A and PAKS 1) and a protease-negative mutant (PAKS 18) which accumulates precursor has shown that there is a change in the outer membrane protein profile in the latter.

Arch Otorhinolaryngol, 1985, 242(3), 273 - 7
Pseudomonas labyrinthitis; Tanaka K et al.; Pseudomonas aeruginosa is the gram-negative bacterial rod which is often isolated from chronic aural discharge . This microorganism may also cause necrotizing infection of the external auditory canal in certain patients with impaired host-defense mechanisms . Involvement of the inner ear by this microbe is extremely rare . In this communication, we report a case of pseudomonas labyrinthitis which resulted from traumatic middle ear injury . Infection produced massive granulations and extensive bone destruction of the otic capsule . This case shows that while P.aeruginosa is usually an avirulent opportunistic pathogen, it may also cause a highly destructive labyrinthitis if the inner ear is entered.

Arzneimittelforschung, 1985, 35(1A), 343 - 8
Synthesis and antibacterial activity of pyrimidinylureidopenicillins; Wetzel B et al.; The 6R-{(R)-2-{3-{5-pyrimidinyl}ureido}-2-(4-hydroxyphenyl) acetamido}-penicillanic acids (10), prepared by two synthetic routes, exhibit broad antimicrobial activity against Gram-positive and Gram-negative bacteria . Their structure activity relationships are discussed . 6R-{(R)-2-{3-{2-(p-Aminosulfonyl)anilino-4-hydroxy-5-pyrimidinyl} ureido}-2-(4-hydroxyphenyl)acetamido}-penicillanic acid, sodium salt (VX-VC 43, 10m), the most active compound, shows very low MIC (minimal inhibitory concentration) values against clinically important Gram-negative bacteria, primarily Pseudomonas aeruginosa.

Drugs, 1985, 29 Suppl 5, 154 - 61
Human pharmacokinetics and antimicrobial activities of the temocillin epimers; Guest EA et al.; The pharmacokinetics of the epimers of temocillin were investigated in 4 healthy male subjects following intravenous administration of 1g of temocillin disodium (free acid) which contains a R : S epimer ratio of approximately 65 : 35 . The R epimer had a 2-fold greater total plasma clearance, a 23% larger volume of distribution and a shorter beta half-life than the S epimer . Intermediate values were obtained for total temocillin (R + S) from high pressure liquid chromatography (HPLC) data . In each plasma sample, the unbound fraction of the R epimer was generally 2-fold higher than that of the S epimer, which is suggested as the reason for the differences in the pharmacokinetic properties of the epimers . The temocillin pharmacokinetic parameters obtained from the microbiological assay data reflect most closely those for the R epimer derived from HPLC data . The resolved R epimer exhibited twice the potency of the S epimer against the microbiological assay organism Pseudomonas aeruginosa NCTC 10701 . However, in tests for antibacterial susceptibility, for instance minimum inhibitory concentration (MIC) determinations involving prolonged incubation, there was little difference in the inhibitory activities of the resolved R and S epimers compared with temocillin (R + S), presumably as a consequence of the epimerization of the individual epimers . In contrast, in rapid tests for bactericidal activity, which minimise the effect of epimerization, the R epimer exhibited greater bactericidal activity than the S epimer.

Jpn J Antibiot, 1985 Jan, 38(1), 83 - 94
{The choice of antibiotics for prophylaxis of postoperative infections in the field of orthopaedics . Clinical experience with cefoxitin}; Doi K et al.; The clinical effects of cefoxitin (CFX) were evaluated in the prophylaxis of postoperative infections in the field of orthopaedics . The clinical response was good in 46 out of 50 patients; an efficacy rate of 92% . Four patients (8%) who did not respond to CFX were suffering from infections due to Mycobacterium tuberculosis (1), suspected Pseudomonas aeruginosa (1), and infection of unknown organism (2) . A review was also made of recent trends among clinically isolated bacterial strains and their susceptibility to antibiotics in the field of orthopaedics . CFX is recommended as an antibiotic of first choice for the prophylaxis of postoperative infections in the field of orthopaedics.

Infection, 1985 Jan-Feb, 13(1), 20 - 6
Moxalactam and piperacillin: a study of in vitro characteristics and pharmacokinetics in cancer patients; Drusano GL et al.; We evaluated the microbiologic characteristics including MIC determinations, synergy plate assays and serum bactericidal activity for two regimens being examined as empiric antibiotic therapy for febrile granulocytopenic cancer patients . The regimens consisted of moxalactam (4 g.i.v . q12h) plus piperacillin (75 mg/kg i.v . q6h) or moxalactam (as above) plus amikacin (levels adjusted to one hour post-infusion levels of 25 mg/l and troughs of 6-8 mg/l) . Detailed pharmacokinetics were ascertained for the beta lactams . All drugs were active against a panel of 11 strains each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus . The pharmacokinetic profile showed serum levels sufficient to provide good antimicrobial activity throughout the dosing interval . Both regimens displayed synergistic or partially synergistic activity in the main for the test organisms; moxalactam plus piperacillin produced good results against S . aureus and P . aeruginosa . In the serum bactericidal assays, the moxalactam-piperacillin combination produced significantly higher mean titers at both peak and trough when compared to the moxalactam-amikacin regimen . This may be because moxalactam acts as a beta lactamase inhibitor for both staphylococcal beta lactamase, as well as the Sabath-Abraham Id type beta lactamase carried by P . aeruginosa (among others) . Moxalactam-piperacillin deserves extensive evaluation as empiric therapy for the febrile neutropenic cancer patients.

J Infect, 1985 Jan, 10(1), 60 - 4
Disseminated infection associated with corticosteroid therapy after transduodenal sphincteroplasty; Sharma BK et al.; Treatment with oral prednisolone appears to have precipitated an episode of ascending cholangitis in an asymptomatic 55-year-old patient . He had undergone a Polya partial gastrectomy, a cholecystectomy and a sphincteroplasty 19, 6 and 2 years earlier, respectively . The cholangitis was complicated by septicaemia with six different enteric organisms including aerobes and anaerobes . He developed liver and lung abscesses, and an indolent Pseudomonas aeruginosa septic arthritis of both hip joints . The patient eventually made a complete recovery, but required surgical replacement of both hips.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 313 - 21
Combination antibiotic therapy: comparison of constant infusion and intermittent bolus dosing in an experimental animal model; Mordenti JJ et al.; To determine the effect of the mode of administration on antibiotic efficacy, 300 neutropenic rats were infected intraperitoneally with an LD-70 inoculum of Pseudomonas aeruginosa and treated with synergistic combinations of amikacin and ticarcillin by intermittent or constant infusion technique . The treatment regimens were designed to provide the same peak serum concentrations that would be observed in humans receiving these drugs . Drug administration over the 24-h period was controlled to ensure that intermittent and constant infusion techniques achieved the same area under the serum concentration/time curves . Based on cumulative mortality at 96 h and viable bacterial cell counts at the site of inoculation constant infusion of both antibiotics produced the best therapeutic results.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 283 - 91
Comparative analysis of the antimicrobial action of polymorphonuclear leucocytes in vitro, ex vivo and in vivo; Dalhoff A et al.; A comparative study on the phagocytic capacity of human and rat polymorphonuclear leucocytes was performed . The activity of rat leucocytes was assessed by using the rat polyvinyl sponge model and the granuloma pouch model . Isolated human leucocytes were either suspended in buffer or homologous serum . Assessments of the susceptibility of Pseudomonas aeruginosa or Klebsiella pneumoniae to the antimicrobial action of leucocytes revealed that the activity of normal human leucocytes and rat leucocytes was very similar, whereas human leucocytes obtained from chronically infected patients were significantly more active . Pretreatment of the bacteria with subinhibitory mezlocillin and azlocillin concentrations with or without immunoglobulin G rendered the bacteria more susceptible to the antimicrobial action of both types of leucocytes . Again results obtained by the different methods were very similar.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 227 - 32
Bactericidal effects of amoxycillin/clavulanic acid and ticarcillin/clavulanic acid in in-vitro kinetic models; White AR et al.; The bactericidal effects of amoxycillin and ticarcillin in the presence of clavulanic acid against beta-lactamase-producing bacteria were investigated in in-vitro kinetic models . Amoxycillin/clavulanic acid was rapidly bactericidal as a simulated intravenous 1.2 g bolus dose, against a strain of Klebsiella pneumoniae highly resistant to amoxycillin . Similarly, ticarcillin/clavulanic acid at concentrations similar to those achieved with a 30 min iv infusion of ticarcillin/clavulanic acid (5.0 g/200 mg) produced bactericidal effects against a ticarcillin-resistant strain of Pseudomonas aeruginosa . Addition of gentamicin to the system resulted in a further enhancement of activity.

J Antimicrob Chemother, 1985 Jan, 15(1), 123 - 5
Meningeal penetration of apalcillin in man; Raoult D et al.; We have used high performance liquid chromatography to evaluate the meningeal penetration of apalcillin . In subjects without meningitis the penetration was poor and the levels obtained did not exceed 1.75 mg/l . In cases of meningitis, when the spinal fluid albumin level was greater than 0.60 g/l, the levels varied from 5 to 30 mg/l . These figures are in accord with those obtained in cases of experimental meningitis . A dosage of 200 mg/kg/day should allow the treatment of meningitis due to sensitive bacteria and in particular due to Pseudomonas aeruginosa.

Am J Clin Pathol, 1985 Jan, 83(1), 130 - 1
False localization of site of endocarditis by cardiac catheterization with quantitative cultures; Bennish M et al.; The authors present a patient with relapsing Pseudomonas aeruginosa endocarditis in whom cardiac catheterization with quantitative cultures falsely localized the infection to the tricuspid valve, probably because the patient was having intermittent rather than continuous bacteremia . After catheterization the patient developed mitral insufficiency and congestive heart failure . This experience suggests that quantitative cultures during cardiac catheterization may give misleading results and that the procedure may have significant complications.

Rev Argent Microbiol, 1985, 17(3), 145 - 8
{Hemorrhagic pneumonia caused by Pseudomonas aeruginosa in mink in Argentina}; Martino P et al.; This work describes the first Haemorrhagic Pneumonia cases in minks not only from Argentina, but from South hemisphere as well . Epidemiology, symptomatology and macro and microscopic lesions found were similar to those described in other countries . The diagnosis was done by isolation of Pseudomonas aeruginosa in large numbers from affected lungs, and serotype no . 6 (Difco system) was the most frequent . Haemorrhagic Pneumonia was experimentally reproduced after infecting intranasally narcotized minks.

Rev Argent Microbiol, 1985, 17(2), 89 - 96
{Proteolytic and elastase activities of Pseudomonas aeruginosa}; Moneto de Ledesma AM et al.; We studied 20 strains of Pseudomonas aeruginosa in its ability to produce proteolytic enzymes . Three different culture media were used: one containing salts and yeast; another one, the dialysed brain-heart-broth fluid and the third, brain-heart-broth . The best was the last one . The purification of the enzymes was performed by precipitation with ammonium sulphate and Sephadex G--100 gel filtration . The number of enzymes acting on casein were demonstrated by means of zymogram previously separated by polyacrylamide gel electrophoresis (Fig . 2) . All the strains acted on gelatin and 80% of them on elastin . 80% of the 20 strains studied showed a correlation between the activity on elastin and the activity on casein (Fig . 1) . 25% of the strains showed the presence of two enzymes using zymogram and 75% only one enzyme . The results were independent of the culture medium used . Strains recently isolated showed to produce a high level of proteolytic enzymes . When the strains were kept in the laboratory the activity decreased to low levels until almost disappeared (Fig . 1) . When the recently isolated strains showed two proteolytic enzymes by zymogram, the less active one disappeared throughout the time when kept in the laboratory . The composition of the purified enzymes were proteic in nature; neither lipoprotein nor glycoprotein were evidenced.

Drugs Exp Clin Res, 1985, 11(4), 247 - 51
N-formimidoyl-thienamycin and norfloxacin against multiple-resistant Pseudomonas aeruginosa strains . Combined in vitro activity and comparison with 14 other antibiotics; Martino P et al.; The in vitro susceptibility of 54 multiple-resistant strains of Pseudomonas aeruginosa to 16 antipseudomonal agents were determined . The majority of these organisms were also beta-lactamase-producing strains . Norfloxacin, N-formimidoyl-thienamycin and aztreonam showed the best antipseudomonal activity, with minimum inhibitory concentrations for 90% of isolates (MIC90) of 2, 8, and 8 mg/l respectively . Of the aminoglycosides, only amikacin (MIC90 = 32 mg/l) showed satisfactory activity, whereas among beta-lactam antibiotics, cefotaxime, ceftriaxone and moxalactam (MIC90 = 32 mg/l) were more active than cefoperazone (MIC90 = 128 mg/l), cefsulodin (MIC90 = 128 mg/l), piperacillin (MIC90 = 512 mg/l) and azlocillin (MIC90 = 1024 mg/l) . A synergistic or partially synergistic interaction (fractional inhibitory concentration index less than 1) was demonstrated in vitro against 37% of the strains when N-formimidoyl-thienamycin was combined with norfloxacin.

Drugs Exp Clin Res, 1985, 11(4), 241 - 5
Antibacterial activity in vitro of sulbenicillin against mucoid and non-mucoid strains of Pseudomonas aeruginosa; Eftimiadi C et al.; The in vitro antibacterial activity of sulbenicillin against a number of mucoid and non-mucoid strains of Pseudomonas aeruginosa was investigated and compared with that of some other beta-lactam antibiotics . From the data reported it is evident that sulbenicillin showed better anti-microbial activity than carbenicillin in almost all the tests run . Sulbenicillin appears to have a somewhat lower activity than piperacillin and cefotaxime; however, cefotaxime and particularly piperacillin are highly conditioned by the inoculum size and have a less favourable MBC to MIC ratio.

Ann Med Interne (Paris), 1985, 136(8), 629 - 33
{Septicemia caused by Pseudomonas aeruginosa serotype O 16 in a hemato-oncology department . Review of 17 cases}; Campillo B et al.; Seventeen cases of Pseudomonas aeruginosa serotype O 16 septicaemia in patients with immune deficiencies are reported . All patients had a poor prognosis from the onset because of the advanced stage of their illness, the particular clinical form of their disease or because of the confirmed inefficacy of their anti-leukaemic chemotherapy . The neutrophil leukocyte count was less than 0.5 X 10(9)/l in all cases and 13 patients had also received wide-spectrum antibiotic therapy for at least 15 days . The septicaemia was accompanied by pelvic sepsis in 6 cases . The prognosis was very poor and 12 patients died rapidly in a state of shock . P . aeruginosa was an infrequent cause of infection during the 31 months period of observation but the O 16 serotype was the commonest in our department . The source of contamination seemed to be a chronic carrier state . P . aeruginosa is resistant to most of the antibiotics which would be expected to be effective.

Complement, 1985, 2(4), 230 - 4
Human plasma fibronectin effect on serum-mediated uptake of Pseudomonas aeruginosa PA 1348A by human granulocytes; Boulanger MJ et al.; The effect of human plasma fibronectin on human granulocyte (PMN) phagocytosis of one strain of Pseudomonas aeruginosa (PA 1348A) was examined in a previously defined optimal phagocytic assay . Normal and fibronectin-deficient serum demonstrated similar rates of bacterial uptake by PMNs . Complement depletion of both sera inhibited phagocytosis . Addition of purified fibronectin did not alter phagocytosis . These findings strongly support the conclusion that fibronectin neither promotes nor inhibits opsonization for phagocytosis of this strain of P . aeruginosa.

Zentralbl Mikrobiol, 1985, 140(8), 631 - 9
{Comparative cytologic studies on the effect of cetyltrimethylammonium bromide on bacterial cells}; Wolfel L et al.; Growing cultures of Pseudomonas aeruginosa and Bacillus megaterium show after treatment with cetyltrimethylammonium bromide (CTAB) typical concentration-dependent alterations of envelope . In Ps . aeruginosa low doses of the detergent cause perforations and lesions of the cytoplasmic membrane, by 0.016% CTAB the formation of extracellular vesicles of the outer membrane ("blebs") and the intracellular assembly of lamellar structures can be detected . These intracellular lamellar structures are artifacts of the cytoplasmic membrane after detergent application . In this case the conglomeration of bacterial cells can be demonstrated with the scanning electron microscope . The results are discussed in connection with the use of CTAB in inactivation and permeabilization of bacteria.

Microbios, 1985, 43(174-175), 193 - 216
Effects of divalent cations on the synthesis of alginic acid-like exopolysaccharide from mucoid Pseudomonas aeruginosa; Dunne WM Jr et al.; The effects of modulated culture calcium (Ca2+) and magnesium (Mg2+) concentrations on the growth of two mucoid Pseudomonas aeruginosa strains of cystic fibrosis origin and on the synthesis of their extracellular polyuronic acids (EPA) were examined . Both strains required a minimum Mg2+ concentration for growth but differed in their Mg2+ requirements to achieve maximum growth potential . The chemical composition of the EPA produced by either strain was not effected by the Mg2+ or Ca2+ concentration of the medium . The exopolysaccharide of strain PM1 was polymannuronic acid and acetylated polymannuronic acid for strain PM9 . However, the molecular size of the exopolysaccharide produced by strain PM1 alone was markedly influenced by culture Ca2+ and Mg2+ levels . When the Mg2+ concentration was 3.0 mM or above, the exopolysaccharide was monodispersed and of high molecular weight . At lower Mg2+ concentrations the polymer was degraded . The evidence suggests that exopolysaccharide degradation resulted from the release or activation of an enzyme in response to reduced Mg2+.

Arch Immunol Ther Exp (Warsz), 1985, 33(4), 507 - 13
Depression by slime-extract from Pseudomonas aeruginosa of delayed type hypersensitivity to sheep erythrocytes; Maresz-Babczyszyn J et al.; High doses of slime-extract from Pseudomonas aeruginosa was found to suppress the delayed type hypersensitivity response to sheep erythrocytes when administered intraperitoneally 1 to 3 days before or 3 days after intravenous sensitization of mice . Moreover, the spleen cells from sensitized and slime-extract treated mice transferred the depression to normal recipients . Inhibition of DTH response was also seen when recipients were injected with slime-extract 24 h before they were infused with spleen cells from donor mice immunized with sheep erythrocytes . The development of skin DTH was quantitated by footpad increase . The data suggest that slime-extract from P . aeruginosa induces in spleens of mice immunosuppressive cells which affect the immunization with sheep red blood cells.

Arch Immunol Ther Exp (Warsz), 1985, 33(4), 499 - 505
Interaction of elastase from Pseudomonas aeruginosa with polymorphonuclear leukocytes and serum; Pajdak E et al.; Interaction of elastase from Pseudomonas aeruginosa 700/75 with polymorphonuclear leukocytes and serum was tested . No difference in phagocytosis by elastase treated PMN and control PMN was noted . Bactericidal activity of serum against P . aeruginosa 700/75 was reduced when serum preincubated with elastase.

Vet Med Nauki, 1985, 22(7), 53 - 61
{Case of Pseudomonas aeruginosa infection in tropical snakes}; Aleksandrov M et al.; Microbiologic and morphologic studies were carried out with there tropical snakes (two Boa constrictor and one Pithon molurus) that contracted the disease and died . Pseudomonas aeroginosa was the only organism isolated from the affected portions of the oral cavity and the lung . It was found that all strains of the species isolated were sensitive to gentamycin, tobramycin, and polymixin B . Up to their death two of the animals were treated with tobramycin with no curative effect whatever . The morphologic lesions were confined to the oral cavity, the lung, and the skin only . Histologically, there were necrotic stomatitis and necrotic exudative pneumonia, diffuse fibrinoid degeneration of the connective tissue within all viscera, deposition of fibrinoid in the walls of the myocardial blood vessels, hyaline droplet degeneration of the hepatocytes and the kidney epithelium, and focal infiltrations of pseudoeosinophile leukocytes in the spleen . It is believed that due to the irreversible injuries of the internal parenchymal organs all treatment in the advanced stages of the disease was ineffective even with the use of antibiotics to which the etiologic agent was strongly susceptible.

Arzneimittelforschung, 1985, 35(8), 1322 - 5
{Susceptibility of Pseudomonas aeruginosa to aztreonam in comparison to other pseudomonas-active beta-lactam antibiotics and gentamicin}; Wundt W et al.; The in vitro activity of aztreonam, a synthetic monobactam, was evaluated against 245 strains of Pseudomonas aeruginosa, 130 of them being recent clinical isolates from patients and 115 from hospital environment . Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and bactericidal kinetics were determined . The possibility of resistance development in vitro was studied . Gentamicin, cefsulodin, piperacillin and azlocillin were used as comparative agents with known antipseudomonal activity . At a concentration of 8 mg/l 83.3%, at 16 mg/l 92% of the tested strains were susceptible to aztreonam . Thus, the activity of aztreonam against Pseudomonas aeruginosa is equivalent to that of gentamicin and cefsulodin and better than that of piperacillin and azlocillin in terms of resistance . Bactericidal kinetics with fourfold MIC, which is equivalent to MBC, are nearly identical for aztreonam, piperacillin and cefsulodin . In vitro induced resistance additionally causes increased resistance against the other beta-lactam antibiotics.

Ophthalmic Res, 1985, 17(5), 289 - 96
Pseudomonas aeruginosa induced ocular infection . A histological comparison of two bacterial strains of different virulence; Hazlett LD et al.; The purpose of this study was to compare and characterize histopathologically the virulence of two bacterial strains in a naturally susceptible animal host . One of the strains Pseudomonas aeruginosa ATCC 19660, routinely used in this laboratory, produces endopthalmitis and phthisis bulbi in C57BL/6 mice within 3-4 weeks . The other bacterial strain, a clinical isolate from a 70-year-old patient with Pseudomonas corneal infection was found to be less virulent in the patient and thus was examined for virulence in the susceptible mouse model . The strain also proved to be less virulent in the normally susceptible mouse when compared with ATCC 19660 . In general, when comparing the histopathological response of the mice to the two bacterial strains, it was found that in contrast to ATCC 19660, fewer polymorphonuclear neutrophils migrated into the cornea at 24-72 h, endothelial and epithelial necrosis was delayed, few free bacteria were observed in the cornea and animals recovered corneal clarity by 21-25 days following infection.

Acta Microbiol Hung, 1985, 32(2), 197 - 200
Enoxacin: a potent inducer of filamentous Escherichia coli cells (a note); Uri JV et al.; Enoxacin (CI-919; AT-2266), a new naphthyridine derivative was found to induce morphologic changes at very low concentrations in Escherichia coli but not in Staphylococcus aureus and Pseudomonas aeruginosa cells . The development of the long filamentous forms observed with nalidixic acid is most probably a consequence of inhibition of DNA synthesis . The phenomenon may, however, not be the sole mechanism of the broad-spectrum antimicrobial activity of enoxacin.

Pediatr Pulmonol, 1985 Jan-Feb, 1(1), 40 - 5
Pseudomonas aeruginosa isolates: comparisons of isolates from campers and from sibling pairs with cystic fibrosis; Thomassen MJ et al.; Sputum or deep throat specimen cultures were obtained from 47 cystic fibrosis (CF) patients residing together at an eight-day summer camp . Pre-camp, initial day, final day and post-camp cultures were obtained and Pseudomonas aeruginosa isolates were characterized by morphology, serotype, pigment production, serum sensitivity, antibiotic susceptibility patterns, hemolysis on blood agar, and CO2 growth requirement . Of the 47 patients, four were not chronically colonized with Pseudomonas and did not become colonized at camp . Analysis of the isolates from the other 43 revealed no significant alteration in the Pseudomonas colonization pattern . Cultures obtained from four sibling pairs among the campers and from 20 additional pairs of siblings revealed that siblings in 20/24 pairs had at least one identical serotype in common . Of the criteria used for characterization, serotyping was the most definitive method for strain identification . Serotyping by both the Homma system and the International system did not detect any serotype at a frequency of more than 31% . In this study, the predominant P . aeruginosa strain of the colonized patients did not change, and non-colonized individuals did not become colonized with P . aeruginosa.

Microbios, 1985, 43(173), 73 - 86
Effects of growth phase and boiling of enteropathogenic Escherichia coli strains on their interaction with Pseudomonas aeruginosa lectins; Glick J et al.; Escherichia coli strains from' serotypes O86, 0128 and O111 varied in their reactivity with Pseudomonas aeruginose lectins (PA-I with D-galactose specificity and PA-II which binds L-fucose, D-mannose, L-galactose and D-fructose) . Generally, cells of O86 strains were agglutinated by PA-I, but not by PA-II, and those of O128 serotype were agglutinated by PA-II, and not by PA-I . Adsorption tests showed that cells of E . coli O86 strains adsorb PA-I to a greater extent than PA-II, while most E . coli O128 strains adsorbed higher amounts of PA-II . Cells of E . coli O111B4 which were not agglutinated by either Pseudomonas lectin could still adsorb both . Boiling of O86 and O128 cells frequently enhanced their agglutinability as well as their lectin adsorption capacity . The agglutinability enhancement was somewhat more prominent in boiled stationary phase cells than in log phase cells probably due to late synthesis of the O antigen components concomitantly with the heat-sensitive components (K antigens) which masked them . PA-I agglutinating activity was inhibited by the lipopolysaccharide (LPS) extracted from E . coli O86 cells, while PA-II was inhibited by the LPS extracted from E . coli O128 cells . These findings indicate that the receptors to the Pseudomonas lectins probably reside in the terminal part of the O-specific-polysaccharide of the LPSs of these bacteria.

Infection, 1985, 13 Suppl 2, S224 - 9
Monoclonal antibodies: technology and application to gram-negative infections; Young LS; Monoclonal antibodies have obvious diagnostic and therapeutic applications in infectious diseases . The technology for producing these highly specific reagents is readily available and we have produced monoclonal antibodies against the core glycolipid (endotoxin) region of gram-negative bacilli and the O-antigens of Pseudomonas aeruginosa . These antibodies are protective by different mechanisms and more than one antibody against a bacterium may give enhanced protection . Use of antibodies plus antimicrobial therapy may yield optimal results.

Infection, 1985, 13 Suppl 2, S185 - 93
In vitro and in vivo effect of immunoglobulin G on the integrity of bacterial membranes; Dalhoff A; The interaction between a modified 7S immunoglobulin (MISG) and bacterial membranes was studied by adopting in vitro as well as in vivo techniques . Preincubation of Escherichia coli and Pseudomonas aeruginosa with MISG resulted in a release of enzymatic markers from the periplasmic space, whereas no cytoplasmic or membrane-bound enzymes were liberated . Due to the interaction of MISG with the outer membrane of gram-negative rods, the bacteria became more susceptible to the antibacterial action of poorly penetrating penicillins because of a significantly increased rate of uptake . These in vitro effects were corroborated under in vivo conditions by adopting the granuloma pouch model . A single intravenous injection of MISG enhanced the therapeutic efficacy of mezlocillin against E . coli; similarly, the antibacterial activity of penicillin G, oxacillin, cephalothin and cefamandole against Staphylococcus aureus was augmented by MISG . These in vivo effects of MISG were not due to an increased rate of phagocytosis or complement activity . Thus, MISG sensitized bacteria to several beta-lactam antibiotics by disorganizing their outer membrane.

Chemotherapy, 1985, 31(5), 351 - 61
Amikacin + ceftazidime therapy of experimental right-sided Pseudomonas aeruginosa endocarditis in rabbits; Bayer AS et al.; We investigated the efficacy of a potent new antipseudomonal beta-lactam agent, ceftazidime, in a model of right-sided Pseudomonas endocarditis in 72 rabbits . Animals received either: no therapy (controls), amikacin (15 mg/kg/day), ceftazidime (100 mg/kg/day) or amikacin + ceftazidime . Amikacin + ceftazidime was significantly more effective than single-drug regimens in terms of reduction of mortality (p less than 0.01), prevention of pulmonary infarction (p less than 0.05), reduction of mean vegetation titers of Pseudomonas aeruginosa (p less than 0.05-p less than 0.0005), sterilization of vegetations (p less than 0.0005) and reduction in prevalence of bacteriologic relapses after therapy (p less than 0.005) . There was no development of resistance in vivo to either amikacin or ceftazidime.

Acta Microbiol Hung, 1985, 32(1), 99 - 106
Characterization of Pseudomonas aeruginosa isolated from drinking water by serogrouping, phage sensitivity and pyocin pattern; Kiss P et al.; Pseudomonas aeruginosa strains isolated in the years 1977-1981 from drinking water samples fell into a large number of epidemiological units determined on the basis of serogroups, phage sensitivity and pyocin pattern . Strains isolated from water were, as a rule, sensitive to more phages than strains cultured from clinical material . The 427 water isolates fell into 8 serogroups and 31 pyocin patterns; 25.1% were untypable by the pyocin method . The frequency of isolation of different phage patterns varied annually . The most frequent epidemiological unit, comprising 9.1% of the isolates, was (serogroup: phage pattern: pyocin pattern) O1: 2/7/16/21/44/68/73/F7/F8/109/119x/352/1214/M4/C11/C18/C21:12 3567; 73.8% of the strains belonged to epidemiological units each represented by less than 4 strains . The large number of epidemiological units indicated that the distribution system had frequently been polluted with P . aeruginosa at different sites, but the organism was unable to invade the whole water supply system.

Folia Microbiol (Praha), 1985, 30(4), 396 - 9
Antimicrobial effect of sugar osazones and anhydro sugars; Zemek J et al.; The antimicrobial effect of 14 sugar osazones and anhydro sugars was studied with model strains of Micrococcus luteus, Bacillus licheniformis, Escherichia coli and strains Staphylococcus aureus and Pseudomonas aeruginosa isolated from clinical material . The relationship between the structure of these compounds, their solubility in water and 1-octanol and antimicrobial effect was investigated.

Chemotherapy, 1985, 31(4), 292 - 6
Comparative antibacterial activities of new beta-lactam antibiotics against Pseudomonas aeruginosa; Fernandes CJ et al.; In vitro activity of nine new cephalosporins and penicillins was determined against 417 isolates of Pseudomonas aeruginosa . Carbenicillin, ticarcillin, gentamicin, tobramycin and netilmicin were also included in the study . Imipenem showed highest activity . More than 90% of the isolates were susceptible to ticarcillin, piperacillin, azlocillin, cefoperazone, cefsulodin and to tobramycin . 57 isolates included in the study were resistant to gentamicin (MIC greater than 4 mg/l); of these, none were resistant to imipenem, and more than 80% were susceptible to piperacillin, azlocillin, cefoperazone and cefsulodin.

Chemotherapy, 1985, 31(4), 255 - 60
Penetration of latamoxef, cefoperazone and piperacillin into the sputum of patients with cystic fibrosis; Laferriere C et al.; Concentrations of latamoxef, cefoperazone and piperacillin, administered intravenously, were measured in serum and sputum of cystic fibrosis patients with recurrent pulmonary infections, chronically colonized with Pseudomonas aeruginosa . Serum pharmacokinetic data were consistent with prior reports . Peak sputum to peak serum concentrations were approximately 3% for each antimicrobial . However, the more prolonged sputum concentrations of piperacillin were reflected in greater areas under the sputum concentration-time curve and a longer duration above the MIC50 of tested P . aeruginosa strains for that drug.

Boll Ist Sieroter Milan, 1985, 64(2), 109 - 14
Water supply as a source of Pseudomonas aeruginosa in a hospital for hematological malignancies; Martino P et al.; This report details of an investigation on a significant increase in nosocomial bacteremias due to multiply-resistant Pseudomonas aeruginosa strains which occurred in a hematological ward . Serotyping according to Habs method showed a high frequence of the serotype 12 . Control cultures identified in the hospital building water reservoirs the presence of the organism . After disinfection of these water reservoirs, the frequence of nosocomial septicemias caused by serotype 12 Pseudomonas aeruginosa strains on the overall bacteremic episodes declined immediately and showed a declining trend in the following 13 months period . To conclude serotyping of Pseudomonas aeruginosa is a useful epidemiological marker and allows to discover from where the diffusion of the organism responsible of outbreaks starts.

J Hyg Epidemiol Microbiol Immunol, 1985, 29(2), 163 - 7
Phage plaques and autoplaques in Pseudomonas aeruginosa strains; Pillich J et al.; Studies were made on the morphological variety in plaques produced by phage lysis and autoplaques in Pseudomonas aeruginosa strains . The great variability of phage plaque morphology may lead to a confusion with the autoplaques produced spontaneously by P . aeruginosa strains . The production of autoplaques is characteristic of a large number of clinical strains of P . aeruginosa . The appearance of autoplaques may complicate analysis of significant clinical strains of P . aeruginosa.

J Immunoassay, 1985, 6(1-2), 23 - 43
Measurement of human antibody activity against Escherichia coli and Pseudomonas aeruginosa using formalin treated whole organisms in an ELISA technique; Cost KM et al.; Using an ELISA technique, specific IgG and specific IgM antibodies to several strains of Escherichia coli and Pseudomonas aeruginosa were measured in 100 normal adults . The distribution of antibody activity to E . coli was narrow, with mean values less than 0.50 OD units . The one exception was in IgG activity to E . coli O. . Mean values for activity against P . aeruginosa ranged from 0.35 to 0.79 OD units . Significant rank order correlations were found for IgM activity among all E . coli and P . aeruginosa strains . The correlations were less consistent for the IgG activity . This baseline data will be used to monitor antibody activity to these common microbes along with several other parameters in a group of ill surgical patients.

Antibiot Chemother, 1985, 36, 88 - 94
Opsonin-independent phagocytosis of Pseudomonas aeruginosa; Speert DP et al.; Three nonmucoid revertant P . aeruginosa strains from cystic fibrosis patients were phagocytized by human polymorphonuclear leukocytes in the absence of serum . Phagocytosis was inhibited by D-mannose and by mannose-containing sugars . Bacteria killed by heat or ultraviolet irradiation or grown in shaken broth were devoid of pili and resistant to nonopsonic phagocytosis . The mucoid parents of two phagocytosis-susceptible nonmucoid revertant strains were resistant to nonopsonic phagocytosis . The nonmucoid revertants were more hydrophobic in nature than the mucoid parents, but they were comparably piliated . Nonopsonic phagocytosis of P . aeruginosa by human neutrophils appears to be mediated in part by pili . Other factors such as the mucoid coating of certain strains may interfere with this process.

Antibiot Chemother, 1985, 36, 157 - 67
Pseudomonas aeruginosa surface polysaccharide vaccines . New therapeutic approaches from basic research; Pier GB; Surface polysaccharide antigens, expressed by strains of P . aeruginosa, are readily available for interaction with the host immune systems . These interactions could potentially result in development of protective immunity against P . aeruginosa infections . Classic strains of P . aeruginosa isolated from immunocompromised hosts and the environment generally express cell surface LPS antigens containing the serotype determinant . Antibody to these determinants has clearly been shown to be protective in both animals and humans . Immunization with a nontoxic, high molecular weight polysaccharide fraction, obtained from the culture supernate of P . aeruginosa, results in the induction of high titered, functional antibody against the type specific determinant . In addition, experimental protocols in animals have shown that a T cell-mediated immunity against type specific antigens can also provide protective immunity . Although the role of T cell-mediated immunity in protection against P . aeruginosa infections is unclear, it may be important in augmenting antibody-mediated protection . P . aeruginosa isolates from CF patients generally do not express type-specific antigens . They do, however, express a different cell surface polysaccharide, MEP . Antibody to this material is made by the colonized CF host, but it clearly is not associated with protective immunity . Animal antibody raised to this material is able to mediate opsonic killing of mucoid strains of P . aeruginosa . Therefore, the antibody response to MEP made by the CF patients may be non-opsonic, or if opsonic, may indicate that antibody to this antigen is not protective in CF patients . Antibody to MEP is able to interact with a low level of human complement for opsonic killing, suggesting that this antibody may be of use in the lung of the CF patient, where complement components may be either low or inactive.

Antibiot Chemother, 1985, 36, 147 - 56
Prospects for a mucoid exopolysaccharide vaccine for the prevention of infection due to mucoid strains of Pseudomonas aeruginosa; Baltimore RS; The problem of infection with MPA is virtually limited to pulmonary infection in patients with CF . Conventional vaccine strategies may not be appropriate because the pathogenesis and epidemiology of the infection is so different from the usual acute bacterial infections . MPA strains appear to be suited to long-term parasitism of immune hosts so initial prevention of colonization may be a necessary function of a vaccine . Since infected hosts have antibody to many antigenic components of PA, vaccines which have been used for PA up until now may not have any protective effect for patients with CF . If the switch from NMPA to MPA colonization in vivo is due to the development of host immunity, some vaccines could conceivably promote infection with MPA . A vaccine which produces antibody to the alginate-like mucoid exopolysaccharide might, however, discourage colonization with MPA and studies of this strategy should be promoted.

Antibiot Chemother, 1985, 36, 134 - 46
Characterization of mouse monoclonal antibodies directed against Pseudomonas aeruginosa lipopolysaccharides; Sadoff JC et al.; Mouse monoclonal antibodies that react with O-side chain specific, O-side chain cross-reactive, and core P . aeruginosa lipopolysaccharide determinants have been isolated . The monoclonals directed at O-side chain determinants are generally opsonophagocytic with human neutrophils and human complement . They also protect mice from intraperitoneal and intravenous challenge and protect in the burned rat model of infection.

Antibiot Chemother, 1985, 36, 13 - 22
Genetics of exopolysaccharide production by mucoid Pseudomonas aeruginosa; Ohman DE et al.; The secretion of the exopolysaccharide, alginate, is believed to contribute to the predilection for persistence of P . aeruginosa in respiratory tract infections of cystic fibrosis patients . To understand more about the pathway of alginate biosynthesis, we have cloned a gene, alg-50, which is involved in alginate biosynthesis . The alg-50 gene was physically mapped on a DNA fragment from P . aeruginosa by deletion analysis and transposition mutagenesis . The alginate trait is unstable, and another clone was found which may contain genes involved in this phenomenon . The two uronic acid components in alginate can vary, and a gene was cloned which increases the L-guluronate concentration of alginate produced by P . aeruginosa.

Cell Tissue Res, 1985, 240(2), 461 - 5
Stimulus-permeability coupling in rat pulmonary macrophages challenged by Pseudomonas aeruginosa . An X-ray microanalysis study; Smith NK et al.; Electron probe X-ray microanalysis (XRMA) of freeze-dried ultrathin sections provides the capability of measuring intracellular elemental content . This methodology was used to investigate the stimulus-permeability coupling responses associated with phagocytosis of Pseudomonas aeruginosa by cultured pulmonary alveolar macrophages (PAMs) of rats . PAMs were challenged with P . aeruginosa suspended in Gey's buffer at a bacteria to PAM ratio of 50:1 for 1 h at 37 degrees C . A 1-mm3 pellet of the unchallenged control PAMs, challenged PAMs and P . aeruginosa alone was quench-frozen in nitrogen-cooled, liquid propane, and 0.1-micron cryosections were cut at -100 degrees C . X-ray spectra were collected for nucleus and cytoplasm of 39 control PAMs, 36 challenged PAMs and 40 P . aeruginosa . Concentrations (mmole/kg dry weight) were obtained for Na, Cl, K, Ca, Mg, P, S for each cell . In the control PAMs, the content was similar to other mammalian cells . Moreover, there were no differences in elemental content between nucleus an cytoplasm . In the challenged PAMs, Na concentration was 4 times that of control PAMs (p less than 0.001) whereas Cl was double (p less than 0.001), K was 29% lower (p less than 0.001), and Ca was 4 times higher (p less than 0.05) . The elemental concentration profile in the P . aeruginosa was distinctly different from that of the PAMs: higher Na, Ca, Mg, but lower Cl and K values . These results demonstrated elemental content changes in cultured PAMs challenged with P . aeruginosa that indicate a stimulus-permeability response by membranes associated with the phagocytic process.

Chemotherapy, 1985, 31(2), 102 - 11
Latamoxef in combination with aminoglycosides against Pseudomonas aeruginosa: similarity with ticarcillin; Sears SD et al.; The in vitro effect of latamoxef against 50 clinical strains of Pseudomonas aeruginosa was compared to that of ticarcillin, both alone and in combination with the aminoglycosides gentamicin, tobramycin and amikacin . Alone, the MIC90 of latamoxef was consistently one-half the MIC90 of ticarcillin . The two antibiotics appeared similar in regard to inoculum effect and bacterial killing . Adding of one-quarter the minimum inhibitory concentration of the aminoglycoside antibiotic to the beta lactam caused reduction in MIC90 of the latter (either ticarcillin or latamoxef) by one-half and decreased the MIC50 by almost one-quarter the concentration required by the beta lactams singly . Therefore, latamoxef singly or in combination with aminoglycosides behaved similarly but was more active than ticarcillin . Using combinations of antibiotics likely to be achieved in the serum of patients, a beneficial in vitro effect (either additive, partially synergistic or synergistic) generally occurred for the beta lactam-aminoglycoside combination if the strain was relatively sensitive to the aminoglycoside used in this combination . It occurred much less frequently for the highly aminoglycoside-resistant isolates.

Antimicrob Agents Chemother, 1985 Jan, 27(1), 1 - 3
In vitro studies of investigational beta-lactams as possible therapy for Pseudomonas aeruginosa endocarditis; Zar FA et al.; The inadequacy of the present medical therapy of Pseudomonas aeruginosa endocarditis prompted an investigation of the in vitro activities of aztreonam, cefsulodin, and imipenem compared with that of ticarcillin against 37 strains of P . aeruginosa isolated from patients with endocarditis . Inhibitory and bactericidal activities were studied for each beta-lactam alone and in combination with tobramycin . All agents showed excellent inhibitory activity . Imipenem was the most inhibitory beta-lactam yet lacked inhibitory synergy against 95% of the strains and bactericidal synergy against 62% . Tolerance to imipenem was seen in six strains . Aztreonam alone was bactericidal against 46% of the strains (at 16 micrograms/ml) and showed bactericidal synergy in 70% . Cefsulodin alone was even less active but similar to aztreonam synergistically . Ticarcillin and tobramycin inhibited all strains as single agents and showed universal bactericidal synergy in combination . None of the new beta-lactams showed consistent superiority to the presently used agent, ticarcillin.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 27 - 36
Effect on growth curve patterns of brief exposure of bacteria to different concentrations of beta-lactam antibiotics; Yourassowsky E et al.; The effect of a brief beta-lactam action on a bacterial culture has been studied by combining the use of a high performance photometer with phase contrast microscopic examination . After exposure of the culture with the antibiotic, the growth curves presented in logn OD have shown the importance of the pre-lytic increase in OD (PIOD) . Using Escherichia coli a study of the PIOD values allowed us to separate the beta-lactam antibiotics studied into two groups: those whose PIOD were concentration-dependent (ampicillin, carbenicillin, ticarcillin, moxalactam, ceftazidime, cefsulodin, cefotaxime) and those whose PIOD were concentration-independent (or weakly dependent) (azlocillin, mezlocillin, piperacillin) . When the PIOD was independent of the concentrations, long filaments were observed by phase contrast microscopy . Using Pseudomonas aeruginosa, all the antibiotics studied produced PIOD values that were barely dependent of the concentrations, and long filaments were observed by phase contrast microscopy . Study of the lag of regrowth in the post antibiotic period using a beta-lactamase technique showed that, if the PIOD was hardly concentration dependent, so was the lag of regrowth.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 265 - 71
Post-MIC effect of fosfomycin on Pseudomonas aeruginosa in vitro and in experimentally infected mice; Haag R; When two strains of Pseudomonas aeruginosa were subjected in vitro to decreasing fosfomycin concentrations in liquid cultures a half-life dependent delay of regrowth occurred after concentrations had fallen below the MIC (post-MIC effect) . There was no post-MIC effect at the short half-lives corresponding to those normally found in mice . However, in similar experiments with surface cultures a post-MIC effect could also be demonstrated at short half-lives . No post-MIC effect, with reference to serum concentrations, could be found in mice infected with the same strains either in a septicaemia or infected thigh model.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 221 - 6
Use of an in-vitro kinetic model to study antibiotic combinations; Zinner SH et al.; A two compartment pharmacokinetic model was used to study combinations of piperacillin with N-formimidoyl thienamycin or amikacin, and azlocillin with netilmicin against strains of Pseudomonas aeruginosa . Antibiotic antagonism seen with in-vitro static tests of piperacillin and thienamycin did not occur with the kinetic model . Piperacillin plus amikacin showed enhanced activity, and azlocillin prevented bacterial regrowth seen with netilmicin alone during multiple dosing experiments at high bacterial inocula . This model is useful in the study of antibiotic combinations.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 201 - 6
In-vivo assessment of in-vitro killing patterns of Pseudomonas aeruginosa; Gerber AU et al.; Time-kill curves of Pseudomonas aeruginosa exposed to gentamicin or ticarcillin in vitro were correlated with time-kill curves obtained with various dosage schedules of the same study drugs in granulocytopenic mice . An instantaneous, fast and drug-dependent killing pattern was found in vitro with gentamicin . This pattern corresponded to bacterial killing in vivo which was clearly dependent on peak drug levels . In contrast, slow bacterial killing with little relationship to concentration was found in vitro with ticarcillin and proved to correlate with an antibacterial effect in vivo seen at trough levels . We conclude that in-vitro time-kill curves of antimicrobial agents may be predictive for optimizing dosage regimens in vivo.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 169 - 73
Computer-controlled in-vitro simulation of multiple dosing regimens; Ledergerber B et al.; The bactericidal effect of gentamicin on Pseudomonas aeruginosa ATCC 27853 was investigated in a computer controlled dynamic in-vitro model, which allows the simultaneous simulation of three different dosing regimens for several days . The same total dose reduced cfu-counts of Pseudomonas aeruginosa most effectively, when administered with peak concentrations of 32 mg/l every 32 h, whereas the other dosing regimens with peak concentrations of 16 mg/l every 16 h and 8 mg/l every 8 h were distinctly less effective following the second and subsequent doses . It was shown that the use of a microcomputer facilitates the in-vitro investigation of multiple dosing regimens but counting of cfu cannot be substituted by automatic measurements of turbidity when rapid bactericidal effects occur.

Folia Microbiol (Praha), 1985, 30(1), 25 - 9
Purification and characterization of pyocins from Pseudomonas aeruginosa; Al-Shibib A et al.; Three types of pyocins were found in Pseudomonas aeruginosa strain 986 and named pyocin type P25, P50, and P70 . Production of these types was inducible by UV irradiation . Their molar mass was estimated . The pyocins obtained were different from the known pyocins R, S, and F in their chemical and physical properties . No immunological cross reaction was observed among these pyocins.

Eur J Respir Dis, 1985 Jan, 66(1), 31 - 9
Inflammatory responses to Pseudomonas aeruginosa and Staphylococcus aureus in the murine lung; Sordelli DO et al.; The changes in pulmonary cell population in response to aerosols containing either Pseudomonas aeruginosa or Staphylococcus aureus were studied in a murine model . The lungs of inbred DBA/2J mice received an inoculum of 2 X 10(5) colony-forming units of the microorganism and lung lavages were performed at various time intervals thereafter . P . aeruginosa aerosols produced an immediate decrease in the number of resident alveolar macrophages (AM), followed by a two-waved recruitment of cells into the respiratory tract; the first wave was composed of polymorphonuclear leukocytes (PMN) and the second of monocyte-like peroxidase-positive AM . The change in cell populations was transient and returned to baseline values within a week after aerosolization . In contrast, aerosolized S . aureus initially induced a slight increase in mononuclear cells, and by 60 min after aerosol exposure, the cell population was not different from that of control animals.

J Antimicrob Chemother, 1985 Jan, 15(1), 9 - 15
Binding of latamoxef (moxalactam) and its decarboxylated derivative to Escherichia coli and Pseudomonas aeruginosa penicillin-binding proteins; Labia R et al.; The binding of latamoxef (moxalactam) and of a decarboxylated derivative to Escherichia coli and Pseudomonas aeruginosa penicillin-binding proteins (PBPs) was measured by competition experiments with 125I-radiolabelled penicillin X . Latamoxef and the decarboxylated derivative were highly bound to most of the PBPs, with the exception of PBP-2 . As the two compounds possess a phenolic side-chain, they also could be radiolabelled with 125I . The proteins thus labelled by these derivatives were qualitatively the same as those labelled by 125I-penicillin X, except for PBP-2 which was not labelled by the iodo derivatives of latamoxef and its decarboxylated derivative, and PBP-1c (in E . coli) which is labelled only poorly by the radioactive penicillin . No important difference between latamoxef and its decarboxylated derivative was found, and the same observation was made for penicillin G and carbenicillin . Thus, it was concluded that the carboxylic group of latamoxef does not play an important role in affinity for the targets.

Genetika, 1985 Jan, 21(1), 39 - 45
{Isolation and analysis of Pseudomonas aeruginosa PAO mutants resistant to nonlysogenic bacteriophages}; Kulakov LA et al.; Nonlysogenizing Pseudomonas aeruginosa PAO bacteriophages were studied . According to morphology of the plaques, they were distributed into three groups: phi k, phi m and phi mn . The mutants of P . aeruginosa PAO resistant to these bacteriophages were selected . On the basis of cris-cross resistance analysis of the mutants, a formal scheme of the receptor sites on the P . aeruginosa PAO bacterial cell surface is drawn . It is shown that bacteriophages phi k and phi m use different receptors for their adsorption . The receptors of phi m and phi mn phages are specifically interconnected . Thus, the receptor for phi k phages is connected with the receptor for phage phi 11 . It appears that the receptor for bacteriophage E79 is identical to those of phi m phages . The phi m receptor is of a composite structure: it includes two different receptors used by phi mn phages.

Clin Exp Immunol, 1985 Jan, 59(1), 190 - 6
The effect of Pseudomonas alginate on rat alveolar macrophage phagocytosis and bacterial opsonization; Oliver AM et al.; Alginate obtained from a mucoid strain of Pseudomonas aeruginosa was shown to inhibit the phagocytosis of an isogenic non-mucoid revertant by rat alveolar macrophages . Phagocytosis of Staphylococcus albus, binding of sensitized sheep erythrocytes to Fc receptors and uptake of latex particles were also inhibited . These results suggest that the alginate acts as a barrier, surrounding the macrophage preventing the attachment of bacteria or other particles to the plasma membrane . This conclusion was supported by showing that alginic acid, a polysaccharide from seaweed structurally similar to alginate also inhibited the phagocytosis of non-mucoid Ps . aeruginosa . The alginate also inhibited opsonisation of the non-mucoid revertant by a non-agglutinating hyperimmune serum . It is proposed that alginate confers a selective advantage on mucoid producing forms of Ps . aeruginosa by impairing the host immune response by its action on alveolar macrophages and opsonization of bacteria.

J Dent Res, 1985 Jan, 64(1), 54 - 7
Oral colonization and susceptibility testing of Pseudomonas aeruginosa oral isolates from cystic fibrosis patients; Lindemann RA et al.; Microbial samples from the oral cavities of cystic fibrosis (C.F.) patients and 20 age-matched normal control subjects were characterized . Mucoid variant Pseudomonas aeruginosa was isolated from the tongue, buccal mucosa, and saliva of C.F . patients only . Analysis of the data suggests that the oral cavity is a potential reservoir for this organism . Aspiration and cross-contamination from this reservoir may be important in perpetuating chronic pulmonary infection in C.F . patients . Susceptibility testing was performed on 20 mucoid variant P . aeruginosa oral isolates obtained from the patients according to standardized broth dilution procedures . The in vitro antimicrobial effects of sodium fluoride, stannous fluoride, and chlorhexidine were measured . Analysis of the data suggests that clinically safe and achievable levels of chlorhexidine and stannous fluoride may be antimicrobial.

J Bacteriol, 1985 Jan, 161(1), 458 - 60
Fructose 1,6-bisphosphate aldolase activity is essential for synthesis of alginate from glucose by Pseudomonas aeruginosa; Banerjee PC et al.; We have isolated a mutant of Pseudomonas aeruginosa deficient in fructose 1,6-bisphosphate aldolase activity . This mutant, similar to the mutants deficient in any of the Entner-Doudoroff pathway enzymes, does not allow appreciable alginate formation from glucose and gluconate, but allows alginate synthesis from mannitol and fructose . This suggests that glucose and gluconate must be converted to fructose 1,6-bisphosphate via the Entner-Doudoroff pathway enzymes and fructose 1,6-bisphosphate aldolase.

J Bacteriol, 1985 Jan, 161(1), 249 - 57
Cloning of Escherichia coli and Pseudomonas aeruginosa phosphomannose isomerase genes and their expression in alginate-negative mutants of Pseudomonas aeruginosa; Darzins A et al.; The phosphomannose isomerase (pmi) gene of Escherichia coli was cloned on a broad-host-range cosmid vector and expressed in Pseudomonas aeruginosa at a low level . Plasmid pAD3, which harbors the E . coli pmi gene, contains a 6.2-kilobase-pair HindIII fragment derived from the chromosome of E . coli . Subcloning produced plasmids carrying the 1.5-kilobase-pair HindIII-HpaI subfragment of pAD3 that restored alginic acid production in a nonmucoid, alginate-negative mutant of P . aeruginosa . This fragment also complemented mannose-negative, phosphomannose isomerase-negative mutants of E . coli and showed no homology by DNA-DNA hybridization to P . aeruginosa chromosomal DNA . By using a BamHI constructed cosmid clone bank of the stable alginate producing strain 8830, we have been able to isolate a recombinant plasmid of P . aeruginosa origin that also restores alginate production in the alginate-negative mutant . This new recombinant plasmid, designated pAD4, contained a 9.9-kilobase-pair EcoRI-BamHI fragment with the ability to restore alginate synthesis in the alginate-negative P . aeruginosa . This fragment showed no homology to E . coli chromosomal DNA or to plasmid pAD3 . Both mucoid and nonmucoid strains of P . aeruginosa had no detectable levels of phosphomannose isomerase activity as measured by mannose 6-phosphate-to-fructose 6-phosphate conversion . However, P . aeruginosa strains harboring the cloned pmi gene of E . coli contained measurable levels of phosphomannose isomerase activity as evidenced by examining the conversion of mannose 6-phosphate to fructose 6-phosphate.

Arch Surg, 1985 Jan, 120(1), 78 - 84
Failure of local immunity . A potential cause of burn wound sepsis; Deitch EA et al.; Destruction of the skin barrier by thermal injury removes the major local defense barrier to bacteria . To determine whether a local defect in immunity also existed, the opsonic activity of blister fluid against Staphylococcus aureus and Pseudomonas aeruginosa as well as neutrophil chemotaxis were measured . The results of these studies indicated that blister fluid could not opsonize Pseudomonas . A series of repletion experiments indicated that the opsonic defect for Pseudomonas was not due to the presence of inhibitors but was due to the lack of normal serum factor(s) . Although both the level of immunoglobulins and complement components in the blister fluid was depressed, the cause of the opsoninopathy appeared to be due to local consumption of complement in the burn wounds . In addition to the opsoninopathy, both neutrophil chemotaxis and random migration were also depressed . In conclusion, a burn injury appears to cause severe impairment of both cellular and humoral local immunity, which could predispose these patients to burn wound sepsis.

Arch Surg, 1985 Jan, 120(1), 43 - 8
Mechanisms of action of two new immunomodulators; Waymack JP et al.; Despite antibiotics, infection remains a significant problem in surgical patients . The reasons are multiple, and include acquired immunologic deficiencies that are seen in malnutrition, sepsis, trauma, and burns . Two immunomodulators, thymopentin (TP-5) and CP-46,665, have been shown to improve survival in infectious animal models of such deficiencies . We investigated the mechanism of action in guinea pigs subjected to a burn of 30% of the total body surface area . These animals received 0.3 mg/kg of thymopentin, 0.3 mg/kg of CP-46,665, or saline solution . Neutrophils, macrophages, and serum samples were obtained from the animals and tested for their ability to phagocytose and kill Pseudomonas aeruginosa . The serum was tested for its ability to opsonize Escherichia coli . Thymopentin was found to improve neutrophil function on postburn days 2 and 4 and to improve macrophage function on postburn day 4 . CP-46,665 was found to improve both macrophage function and opsonization on postburn day 2.

Laryngoscope, 1985 Jan, 95(1), 34 - 7
Pseudomonas aeruginosa in chronic maxillary sinusitis; Koltai PJ et al.; Pseudomonas aeruginosa (Ps . Au.) infection of the maxillary sinus has been reported as an incidental finding on routine antrostomy; however, it has also been noted in several studies as the significant organism in the etiology of chronic sinusitis . Four case reports of culture verified Ps . Au . maxillary sinusitis are presented . The therapeutic modality used in two of the cases was a Caldwell-Luc operation and in two, an intranasal antrostomy . In all cases, multiple irrigations through the surgically created nasoantral windows were done postoperatively, as was the instillation of gentamicin ophthalmic drops intranasally . In all four cases the infection cleared with this combined surgical and medical therapy.

J Trauma, 1985 Jan, 25(1), 27 - 31
Synergistic action of silver sulfadiazine and sodium piperacillin on resistant Pseudomonas aeruginosa in vitro and in experimental burn wound infections; Modak S et al.; Silver sulfadiazine-resistant organisms are arising at an irregular rate and may eventually interfere with wound management . To counter this problem several new antibacterial agents were tested in combination with silver sulfadiazine . Only sodium piperacillin (Pipracil, Lederle) exhibited synergism with silver sulfadiazine both in vitro (against various species of organisms) and in burned animals . The MIC of AgSD and Pipracil was 50 nmole/ml and 250 nmole/ml, respectively, but a combination of 6 nmole/ml of AgSD and 7.5 nmole/ml of Pipracil inhibited the growth of Pseudomonas aeruginosa . In burned mice infected with either AgSD-resistant or sensitive strains, the mortality in groups receiving combinations of topical Pipracil and silver sulfadiazine was 0-10%; in contrast, treatment with Pipracil or silver sulfadiazine alone resulted in much higher mortality . Thus it would appear that a combination of silver sulfadiazine and Pipracil, each of which have long been used in patients topically and parenterally, may prove valuable in patients with burn wound infections related to or caused by organisms resistant to silver sulfadiazine.

Clin Ther, 1985, 7(2), 225 - 38
Imipenem/cilastatin therapy of serious infections: a U.S . multicenter noncomparative trial; Calandra GB et al.; Imipenem/cilastatin, which combines a broad-spectrum antibiotic derived from thienamycin with a specific enzyme inhibitor, was administered in dosages of 1 to 4 gm/day to 717 patients in a multicenter noncomparative trial . Ninety-nine percent of the bacterial pathogens tested were susceptible to imipenem, and 86% were eradicated . Clinical outcome was favorable in 85% or more of the cases when assessed according to the site of infection, and 92% of the cases responded to treatment overall . Development of resistance was rare except for Pseudomonas aeruginosa, which became resistant in 19% of the patients infected with that organism . More than half the patients with resistant P aeruginosa had a favorable clinical outcome, however . Superinfection occurred in approximately 4% of all patients . The adverse clinical experiences occurring most frequently were related to gastrointestinal function (nausea, vomiting, and diarrhea) . In general, the safety profile of imipenem/cilastatin was similar to that of other beta-lactam antibiotics.

Urologe A, 1985 Jan, 24(1), 36 - 8
{The perfusate culture--bacteriologic monitoring of kidney grafts}; Buchholz B et al.; Since the kidney recipient's immune system is entirely suppressed, any bacterial contamination from a graft might be hazardous . Major statistics {1,3,4,5} reveal a mortality as high as 10% due to infectious and gastrointestinal complications . From July 1979 to December 1983 114 kidney grafts have been done in our center . After transplantation none of the patients died as a result of complications due to infection . Microbiologic examination of the perfusate is obligatory to detect contamination . It was used in 145 donor nephrectomies; 28% of the perfusate culture samples were positive: In 4 of 5 cases (81%) the bacteria isolated were of the non-pathogenic type seen in the normal flora of the skin (Staphylococcus epidermidis) . Introduction of cover drapes lowered the positive culture rate to 8% . Isolation of S . epidermidis after desinfection of the skin (6x) with 70% spore-free alcohol is proof of the extraordinary sensitivity of the method used . The outstanding clinical importance of this method is the rapid information obtained on any contamination and the early suggestion concerning the first choice of antibiotic . Though E.coli and Pseudomonas aeruginosa were found in the culture, no clinical infection was seen under adequate antimicrobial therapy . Among 114 kidney transplantations in our center no patient died of bacterial infection . Our experience points out that the effect of general antibiotic prophylaxis is negligible . Instead, the effect of early application of antibiotics in accordance with the results of the perfusate culture is superior.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 153 - 7
Activity of imipenem in an in-vitro model simulating pharmacokinetic parameters in human blood; Shah PM; The behaviour of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was studied in human blood, when exposed to imipenem concentrations rising from zero to a maximum of 6.5 mg/l in 1.9 h, and gradually decreasing to below detection level of less than 0.22 mg/l at 12 h . Under these conditions there was a marked bactericidal activity and a long-acting effect of imipenem.

Drugs, 1985, 29 Suppl 5, 78 - 84
A survey of temocillin sensitivity of strains resistant to newer beta-lactam antibiotics; Focht J et al.; The susceptibility of a total of 2014 Gram-negative clinical isolates (except Pseudomonas aeruginosa) to a number of antibiotics, including temocillin, was investigated in 2 geographically distinct areas . Overall, more strains were sensitive to temocillin than to mezlocillin, piperacillin, amoxycillin plus clavulanic acid, cefotaxime, cephazolin, latamoxef (moxalactam), cefoxitin, or netilmicin . Susceptibility to temocillin of multiple-resistant strains was studied.

Infect Immun, 1985 Jan, 47(1), 1 - 4
Role of Pseudomonas aeruginosa mucoid exopolysaccharide in adherence to tracheal cells; Ramphal R et al.; The mucoid exopolysaccharide of Pseudomonas aeruginosa is thought to confer antiphagocytic properties on mucoid strains of P . aeruginosa, thus allowing them to persist in the respiratory tract . It has also been speculated that the mucoid exopolysaccharide may be the adhesin for mucoid strains, but proof is lacking . We studied the role of the mucoid exopolysaccharide in adherence of mucoid strains in competitive experiments with purified mucoid exopolysaccharide, by measuring the binding of 14C-labeled mucoid exopolysaccharide to injured tracheas and testing whether an antibody against the major epitope of the mucoid exopolysaccharide inhibits adherence of these organisms . Our data show that the purified mucoid exopolysaccharide increased the adherence of four of the mucoid strains tested (by 50 to 300%; P less than 0.001) instead of inhibiting adherence . Radiolabeled mucoid exopolysaccharide bound much better to injured tracheal cells than to normal tracheal cells (P less than 0.001), and antibody against the antigen of strain 2192, the strain from which mucoid exopolysaccharide was prepared, inhibited the adherence of four of five mucoid strains but not the strain lacking this antigen . This antibody also failed to inhibit a nonmucoid revertant from strain 2192, which was previously shown to be inhibited by pili . These data strongly support the thesis that the mucoid exopolysaccharide is the adhesion for mucoid strains of P . aeruginosa.

Adv Exp Med Biol, 1985, 185, 223 - 32
Genetic approaches to study Pseudomonas aeruginosa protein antigens; Nicas TI et al.; Pseudomonas aeruginosa produces a large number of extracellular products which may play a role in pathogenesis . We have used genetic techniques to elucidate the relative contribution of these proteins to virulence, and as a method of producing safe toxoids . A mutant has been isolated which produces an immunologically reactive nontoxic form of toxin A, the most toxic extracellular protein produced by P . aeruginosa . Although there are difficulties in production of sufficient quantities of this CRM toxoid, these are likely to be solved by further genetic manipulation . Protection studies with toxin A antibody and studies of mutants deficient in toxin A have confirmed that toxin A plays a role in pathogenesis while clearly showing that toxin A alone cannot totally account for the virulence of P . aeruginosa . Studies of mutants specifically altered in three other products, exoenzyme S, and the two major proteases of P . aeruginosa, elastase and alkaline protease, have clarified the contribution of these products to virulence . Demonstration by genetic studies that exoenzyme S was a major factor in the virulence for one P . aeruginosa strain allowed us to correctly predict that antibody to this product would be protective against infection with that strain.

Mol Gen Genet, 1985, 200(1), 123 - 7
DNA homology and adsorption specificity of Pseudomonas aeruginosa virulent bacteriophages; Kulakov LA et al.; The DNA homology and adsorption specificity of newly isolated virulent bacteriophages of P . aeruginosa have been studied . On the basis of this analysis all phages were divided into four groups: phi k, phi m, phi mnP78-like and phi mnF82-like bacteriophages . DNA's of phi k as well as phi m phages were shown to possess different restriction patterns although they have an extensive homology . Unlike other groups, phi k phages were characterized by the presence of T4 DNA ligase--repaired, single-chain breaks.

Gene, 1985, 33(3), 313 - 21
Orientation and expression of the cloned hemolysin gene of Pseudomonas aeruginosa; Ding J et al.; The structural gene for Pseudomonas aeruginosa hemolysin, carried on recombinant plasmid pSL2 and cloned in Escherichia coli, was analyzed by insertional and deletional mutagenesis . Expression of the hemolysin was blocked by insertion of transposon Tn5 into different locations . Two of the mutants allowed detectable synthesis of truncated hemolysin polypeptides of two different sizes and thus defined the structural gene . The location of the hemolysin gene in the recombinant plasmid, and the direction of transcription, were further established by nuclease BAL 31 digestion, and by construction of gene fusions between hemolysin and beta-galactosidase . Evidently, the tet promoter contributed to the majority of the expression of cloned hemolysin gene, but the Pseudomonas promoter was present in the cloned DNA and was functional in E . coli since inactivation of the tet promoter either by Tn5 insertion or by deletion decreased synthesis of the 80-kDal hemolysin but did not fully abolish it.

Gene, 1985, 33(3), 293 - 303
Transposon insertion mutagenesis of Pseudomonas aeruginosa with a Tn5 derivative: application to physical mapping of the arc gene cluster; Rella M et al.; For insertional mutagenesis of Pseudomonas aeruginosa, a derivative of the kanamycin-resistance (KmR) transposon Tn5 was constructed (Tn5-751) that carried the trimethoprim-resistance (TpR) determinant from plasmid R751 as an additional marker . Double selection for KmR and TpR avoided the isolation of spontaneous aminoglycoside-resistant mutants which occur at high frequencies in P . aeruginosa . As a delivery system for the recombinant transposon, plasmid pME305, a derivative of the broad-host-range plasma RP1, proved effective; pME305 is temperature-sensitive at 43 degrees C for maintenance in Escherichia coli and P . aeruginosa and deleted for IS21 and the KmR and primase genes . In matings with an E . coli donor carrying pME9(= pME305::Tn5-751), transposon insertion mutants of P . aeruginosa PAO were recovered at approx . 5 X 10(-7)/donor at 43 degrees C . Among Tn5-751 insertional mutants 0.9% were auxotrophs . A thr::Tn5-751 mutation near the recA-like locus rec-102 is useful for the construction of recombination-deficient strains . Several arc::Tn5-751 mutants could be isolated that were defective in anaerobic utilization of arginine as an energy source . From three of these mutants the arc gene region was cloned into an E . coli vector plasmid . Since Tn5-751 has a single EcoRI site between the TpR and KmR genes, EcoRI-generated fragments carrying either resistance determinant plus adjacent chromosomal DNA could be selected separately in E . coli . Thus, a restriction map of the arc region was constructed and verified by hybridization experiments . The arc genes were tightly clustered, confirming earlier genetic evidence.

Antibiot Chemother, 1985, 36, 95 - 102
The Pseudomonas aeruginosa outer membrane permeability barrier and how to overcome it; Hancock RE; The intrinsic resistance of P . aeruginosa to most hydrophilic antibiotics can be explained, in part, on the basis of its low outer membrane permeability . Protein F which constitutes the major outer membrane porin protein for the uptake of hydrophilic compounds, is poorly functional . We have demonstrated that less than 1% of the 200,000 or so copies of protein F per cell can form active functional channels . Our working hypothesis is that the species of LPS associated with individual protein F trimers determines whether these trimers adopt a functional conformation . Since low outer membrane permeability constitutes a major problem for the penetration of antibiotics into P . aeruginosa, we have started to search for compounds which permeabilize outer membranes ('permeabilizers') and thus would be potentially synergistic with antibiotics . Eighteen permeabilizer compounds have been discovered and fall into defined chemical groupings including polycations, organic cations and divalent cation chelators.

Antibiot Chemother, 1985, 36, 40 - 8
Contribution of exoenzyme S to the virulence of Pseudomonas aeruginosa; Nicas TI et al.; Exoenzyme S is an extracellular ADPR transferase produced by P . aeruginosa . Forms of this enzyme that have thus far been purified are not toxic, however, exoenzyme S clearly contributes to the virulence of strain 388 . Thus, a Tn1 mutant deficient in exoenzyme S was found to be markedly less virulent than its exoenzyme S-producing parental strain in both a burned mouse infection model and a rat chronic lung infection model . Exoenzyme S does not appear to contribute to initial colonization of the rat lung or the burned mouse skin . Exoenzyme S does, however, appear to contribute to local tissue damage in the rat lung, and to dissemination of P . aeruginosa from the skin into the blood and distant organs of the burned mouse . Perhaps our most important observation is that specific antibody against exoenzyme S confers a high level of protection against subsequent infection of burned mice . While these results must be extended to include additional strains they are encouraging, and they underscore the relative importance of exoenzyme S in the pathogenesis of P . aeruginosa infections.

J Infect Dis, 1985 Jan, 151(1), 15 - 22
Influence of drugs that block calcium channels on the microbicidal function of human neutrophils; Kazanjian PH et al.; The central role of calcium ions in cell physiology prompted us to examine the hypothesis that pharmacological concentrations of calcium channel-blocking drugs might affect human neutrophil (PMN) functions . The capacity of PMNs suspended in verapamil hydrochloride for killing Pseudomonas aeruginosa during two hour incubations was significantly impaired (P less than .05) . Several observations suggested that this drug effect was the result of altered calcium metabolism: exposure to verapamil decreased the uptake of 45Ca++ by PMNs subsequently exposed to the calcium ionophore A23187; verapamil did not impair PMN function in the absence of extracellular calcium; and the addition of A23187 concomitantly with (but not following) verapamil prevented PMN dysfunction . In addition, nifedipine, a structurally dissimilar calcium channel-blocking drug, also impaired the bactericidal activity of PMNs against Pseudomonas aeruginosa (P less than .02) . Further studies revealed that treatment with verapamil did not affect PMN phagocytosis, but significantly impaired the PMN respiratory burst (as shown by superoxide anion generation assay; P less than .05) . We conclude that PMNs exposed to pharmacological concentrations of calcium channel-blocking drugs exhibit a reduced capacity to kill bacteria.

Drugs Exp Clin Res, 1985, 11(5), 343 - 50
Assessment of the in vitro and in vivo activity of ciprofloxacin measured against current standards of therapy; Zeiler HJ et al.; The bactericidal activity of ciprofloxacin in active human serum was investigated using serum-resistant Escherichia coli C14 and Pseudomonas aeruginosa 220 as test organisms . In 100% or 80% human serum the growth rate of E . coli C14 was lower than in broth . This also influenced the killing rate of ciprofloxacin . Ciprofloxacin was more active in serum than norfloxacin or ofloxacin and killed Pseudomonas aeruginosa 220 much more rapidly than azlocillin or tobramycin . Rapid killing was also observed in vivo in the blood of intraperitoneally infected mice, ciprofloxacin being superior to norfloxacin, ofloxacin and sisomicin . In mouse protection studies with E . coli Neumann as infecting organism, the dose-effect ratio showed that, despite extremely low blood concentrations, ciprofloxacin had a full therapeutic effect at a dose of 2.5 mg/kg p.o . or less than or equal to 0.5 mg/kg s.c., whereas cefotaxime, despite similar low MIC values in vitro, had to be administered at a dose of 20 mg/kg s.c . in order to achieve 100% survival . These data indicate that ciprofloxacin is effective at low concentrations both in vitro and in vivo.

Arzneimittelforschung, 1985, 35(10), 1600 - 3
Influence of ciprofloxacin on the ultrastructure of gram-negative and gram-positive bacteria; Voigt WH et al.; Killing curves were performed in pooled active human serum using serum resistant Escherichia coli C14, Pseudomonas aeruginosa 220 and Staphylococcus aureus 25151 as test organisms . Ciprofloxacin (a quinoline-carboxylic acid derivative, Bay o 9867) was added in concentrations of 0.025-4.0 micrograms/ml . Samples were taken at different times to determine the number of viable bacteria and to prepare specimens for transmission electron microscopy . The following drug concentration-dependent results were obtained: In the early phase of the bactericidal process in Escherichia coli C14 distinct loosenings of the peripheral cytoplasm occurred . With Pseudomonas aeruginosa 220 osmiophilic condensations were detected in the less dense areas where the bacterial DNA may be located . At low concentrations, elongation of gram-negative bacterial cells was observed, whereas at higher concentrations rupture and lysis occurred . In staphylococci, severe disturbances of septum formation and surface deformations could be found; in the final stage proteolysis and empty envelopes were observed.

Int Arch Allergy Appl Immunol, 1985, 78(4), 391 - 5
Polyclonal B cell activators inhibit contact sensitivity to oxazolone in mice by potentiating the production of anti-hapten antibodies that induce T suppressor lymphocytes acting through the release of soluble factors; Campa M et al.; Polyclonal B cell activators (PBAs) such as purified protein derivative, lipopolysaccharide, Staphylococcus aureus strain Cowan I (StaCwI), and Pseudomonas aeruginosa inhibit contact sensitivity to oxazolone in mice when given 24 h before sensitization . This suppression, transferable from immunodepressed animals to oxazolone-sensitized recipients with immune serum, has been shown to be due to the early appearance of anti-hapten antibodies . These antibodies elicit T suppressor cells which release soluble factor(s) capable of inhibiting the passive transfer of contact sensitivity.

Comp Biochem Physiol C, 1985, 82(2), 345 - 8
Purification and characterization of an antibacterial factor from snail mucus; Kubota Y et al.; The antibacterial factor from the body surface of the African giant snail, Achatina fulica Ferussac, was isolated by DEAE-Toyopearl 650M ion exchange chromatography . The isolated preparation exhibited highly positive antibacterial activity both for the Gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus and for the Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, but it lost such activity when heated at 75 degrees C for 5 min . The antibacterial factor of the snail mucus was a glycoprotein whose molecular weight (MW) was about 160,000 . It was composed of two subunits of MW 70,000-80,000.

Microbios, 1985, 42(167), 7 - 16
Basic characterization of a Pseudomonas aeruginosa PAO1 bacteriophage; Patel IR et al.; A bacteriophage of Pseudomonas aeruginosa PAO1 was characterized . Bacteriophage PIK was found to adsorb on the cell wall of the host organism . Electron microscopy of the phage PIK revealed that it had a bipyramidal hexagonal prismatic head of 110 nm in diameter, a tail which was 158 nm long and a tail plate of 47 nm width . This paper describes its basic characters, and a quantitative study was made of its adsorption to exponential phase cells of two different strains of P . aeruginosa . PIK was found to contain double stranded DNA and it appears to be virulent towards its host, P . aeruginosa PAO1 . It was classified into the group of phages possessing a contractile tail.

Biomed Pharmacother, 1985, 39(9-10), 477 - 81
Effect of gamma-globulin preparations on phagocytic function of whole blood; Tono-Oka T et al.; Effect of gamma globulin preparations on opsonic activity in whole blood from non-immunodeficiency was studied using chemiluminescence as the parameter of phagocytic function of granulocytes . Poly (ethylene) glycol treated, Fc-intact preparation clearly enhanced chemiluminescence (luminol-dependent) of blood cells phagocytosing zymosan, Escherichia coli (E . coli), or Pseudomonas aeruginosa (P . aeruginosa), but pepsin-treated preparation showed no effect . Whole blood added with intact preparation at the final concentration of 4 mg/ml showed enhanced CL induced by E . coli and P . aeruginosa in many individuals, especially in infancy, although in adult age suppressive effect was often observed . In six patients with pediatric malignancy and three newborns with suspected septicemia, CL induced by E . coli or P . aeruginosa was measured after the administration of 150 mg/kg of intact preparations, and 4/6 of malignancy showed increased CL by E . coli, and all infants showed increased CL by E . coli and P . aeruginosa . These results suggest that intact gamma globulin preparation can increase phagocytic ability of whole blood in non-immunodeficiency via its opsonins, and may justify the administration of intact gamma globulins in non-immunodeficiency for the purpose of treating bacterial infections in some selected cases.

Adv Exp Med Biol, 1985, 185, 215 - 22
Monoclonal antibodies against bacterial outer membrane antigens; Hancock RE et al.; Monoclonal antibodies have proved to be highly specific tools for defining the antigenic epitopes of Pseudomonas aeruginosa outer membrane macromolecules . In this article we have highlighted the use of monoclonal antibodies in the study of lipopolysaccharide heterogeneity and in particular have demonstrated that single monoclonal antibodies can recognize epitopes on lipid A which are conserved in all Gram negative bacteria tested . Monoclonal antibodies against P . aeruginosa outer membrane proteins have been used to demonstrate the strong conservation of specific antigenic sites in all P . aeruginosa strains tested . In the case of one monoclonal antibody, specific for outer membrane lipoprotein H2, the antigenic site recognized by the antibody was also found to be conserved in all group 1 Pseudomonads . The implications of these monoclonal antibodies to bacterial taxonomy is discussed . Monoclonal antibodies against two separate conserved surface epitopes on outer membrane protein F were isolated and differentiated according to their reactions with 2 mercaptoethanol-reduced protein F and with proteolytic and cyanogen bromide peptide fragments of protein F . One of these protein F-specific monoclonal antibodies has been demonstrated to have immunotherapeutic potential.

Infection, 1985, 13 Suppl 2, S194 - 5
Indirect evidence of cell wall alterations in pseudomonas aeruginosa by immunoglobulin preparations; Stubner G; Ten strains of Pseudomonas aeruginosa isolated from different clinical sources were incubated with immunoglobulin preparations for i.v . use . This resulted in the release of beta-lactamases normally cellbound in the periplasmic space . The amount of released beta-lactamases--depending on the degree of cell wall alteration--was spectrophotometrically determined by the use of nitrocefin as an indicator substance . Beta-lactamase release varies according to strain specificity and depends on the chemical modification of the immunoglobulins used.

Am J Med, 1984 Dec 21, 77(6A), 7 - 10
Cefmenoxime in surgical infections: treatment and penetration into peritoneal fluid and wound secretions; Wittke RR et al.; Sixty patients (23 men and 37 women) with a median age of 56.7 years (range 20 to 80) and a median weight of 69 kg were treated with cefmenoxime as short-term perioperative prophylaxis . Patients were undergoing surgery for an infected gallbladder, bile duct, or colon or were being treated for local or diffuse peritonitis and soft tissue infections . Overall clinical efficacy including very good and good results could be achieved in 88.3 percent . Moderate clinical efficacy was achieved in six cases, two of which were due to Pseudomonas aeruginosa . In 38 of 60 patients an antibiogram could be performed before and after therapy . Of the isolated 46 strains, 40 pathogens (86.95 percent) were eradicated during cefmenoxime treatment and in two cases a replacement was observed . After one hour, peak concentrations in serum could be reached with over 70 micrograms/ml.

Carbohydr Res, 1984 Dec 15, 135(1), 147 - 54
The purification and chemical characterisation of the alginate present in extracellular material produced by mucoid strains of Pseudomonas aeruginosa; Sherbrock-Cox V et al.; A rapid ion-exchange method has been used to purify the alginate from the extracellular material of mucoid strains of Pseudomonas aeruginosa isolated from the lungs of cystic fibrosis patients . The structure has been investigated by chemical analysis, infrared spectroscopy, paper chromatography, and gas-liquid chromatography . The alginates contain mainly random or poly(D-mannuronic acid) block structures, and are highly acetylated . The relative viscosity is not correlated with the ratio of D-mannuronic acid to L-guluronic acid residues, or the degree of acetylation . The chemical/physical properties of the alginate from P . aeruginosa are considered in the context of the growth of the organism in the lung.

J Cell Biol, 1984 Dec, 99(6), 1907 - 16
A Chinese hamster ovary cell mutant with a heat-sensitive, conditional-lethal defect in vacuolar function; Marnell MH et al.; We describe a mutant derived from Chinese hamster ovary cells that is offt-sensitive for viability and for resistance to certain protein toxins . This mutant, termed G.7.1, grows normally at 34 degrees C but does not grow in Dulbecco's modified Eagle's medium at 39.5 degrees C . However, when this medium is supplemented with FeSO4, the mutant cells will grow at the elevated temperature . At 39.5 degrees C, G.7.1 cells acquire resistance to diphtheria toxin, modeccin, and Pseudomonas aeruginosa exotoxin A, all of which are protein toxins that require endocytosis and exposure to a low pH within vesicles before they can invade the cytosol and kill cells . The properties of mutant G.7.1 could result from a heat-sensitive lesion that impairs vacuolar acidification . We assayed the ATP-stimulated generation of pH gradients across the membrane of vesicles in cell-free preparations from mutant and parental cells by the partitioning of acridine orange into acidic compartments and found that the acidification response of the mutant cells was heat-labile . Altogether the evidence suggests that G.7.1 cells contain a heat-sensitive lesion that impairs vacuolar acidification and that they fail to grow in normal medium at 39.5 degrees C because they cannot extract Fe+3 from transferrin, a process that normally requires exposing transferrin to a low pH within endosomal vesicles.

Infect Immun, 1984 Dec, 46(3), 631 - 4
Binding of pseudomonal leukocidin to rabbit polymorphonuclear leukocytes; Hirayama T et al.; The leukocytotoxic toxin pseudomonal leukocidin, produced by Pseudomonas aeruginosa, was radioiodinated with chloramine-T reagent . Binding of {125I}leukocidin to rabbit polymorphonuclear leukocytes was found to be concentration dependent at 37 degrees C . A Scatchard plot of binding data was linear, indicating that leukocidin binds to a single population of sites . The dissociation constant, KD, was calculated from the Scatchard plot to be 2.5 X 10(-7) M, and the number of binding sites per leukocyte was approximately 4.4 X 10(5) . Unlabeled leukocidin or antileukocidin antibody reduced the binding of {125I}leukocidin to the leukocytes . A leukocidin-binding protein was extracted from rabbit polymorphonuclear leukocytes with Triton X-100 and purified by leukocidin-Sepharose 4B affinity column chromatography . Approximately 60 micrograms of binding protein was obtained from 8.1 mg of material extracted from the leukocytes . The binding protein had a molecular weight of about 50,000 as shown by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis and staining with silver nitrate . Under nondenaturing conditions, its molecular weight was also about 50,000, as shown by gel filtration-Sephadex G-200 chromatography . The 50,000-dalton protein purified in this way from rabbit polymorphonuclear leukocytes competitively inhibited the binding of leukocidin to leukocytes and inactivated leukocidin activity . With equimolar amounts of the 50,000-dalton protein and leukocidin, up to 90% inactivation of leukocidin was observed.

Arch Inst Pasteur Tunis, 1984 Dec, 61(4), 415 - 25
{Infections and deaths of horned vipers, Cerastes cerastes (L., 1758) and lebetin vipers, Vipera lebetina (L., 1758) caused by Pseudomonas aeruginosa (Schröeter, 1885)}; Slavtchev RS et al.; The authors present some data about the buccal and intestinal microflora of Ophidian Reptiles schooling in the vivaria of the Institute Pasteur of Tunis . They describe two cases of infestation and dead, chiefly symptomatology, of a horned Viper, Cerastes cerastes (L . 1758) and a lebetin Viper, Vipera lebetina (L., 1758) by Pseudomonas aeruginosa Schroeter, 1885.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Dec, (12), 68 - 72
{Comparative evaluation of the pathological process in a model of acute experimental pneumonia in rats caused by Pseudomonas aeruginosa strains of various origin}; Tsinzerling VF et al.; The experimental model of acute pneumonia induced by the intratracheal inoculation of rats with P . aeruginosa strains has been developed; the use of this model permits the quantitative evaluation of the contamination of respiratory organs with this microorganism, as well as the development of schemes for the antimicrobial therapy of P . aeruginosa infection . The correlation between the severity of experimental pneumonia induced by P . aeruginosa and the production of pathogenicity factors by these microorganisms has been revealed.

J Antibiot (Tokyo), 1984 Dec, 37(12), 1681 - 6
Synergistic activity of astromicin and beta-lactam antibiotics against Pseudomonas aeruginosa in vitro and in vivo; Kitaura K et al.; Synergistic activity of astromicin and an antipseudomonal beta-lactam antibiotic such as piperacillin, cefsulodin or carbenicillin against Pseudomonas aeruginosa was demonstrated in vitro and in vivo . Synergy in vitro was observed more often when astromicin was combined with piperacillin or cefsulodin than when it was combined with carbenicillin . The combination of astromicin with piperacillin showed a bactericidal activity against Pseudomonas aeruginosa at a bacteriostatic concentration of each antibiotic alone . The synergy observed in vitro was reproduced against experimental mouse infections, and the astromicin-piperacillin or cefsulodin combination produced significantly greater protective effects than the single use of individual antibiotics.

Arch Dis Child, 1984 Dec, 59(12), 1131 - 4
Prospective, controlled study of a polyvalent pseudomonas vaccine in cystic fibrosis--three year results; Langford DT et al.; Thirty four children with cystic fibrosis allocated to pseudomonas vaccine and control groups were studied for three years . No significant differences were observed in the numbers colonised by Pseudomonas aeruginosa or in the overall disease progress of the two groups.

J Gen Microbiol, 1984 Dec, 130 ( Pt 12), 3101 - 11
Complementation analysis of the aliphatic amidase genes of Pseudomonas aeruginosa; Drew R; A plasmid, pCL34, capable of autonomous replication in Escherichia coli and Pseudomonas aeruginosa has been constructed which carries the promoter and structural gene (amiE) for P . aeruginosa amidase, but not the regulator gene (amiR) . Plasmid pCL34 has been mobilized from E . coli to P . aeruginosa using the broad host range plasmid RP4 . Complementation studies were performed in P . aeruginosa strains carrying various amidase mutations . Measurements of amidase activity in the recipients under inducing, non-inducing and repressing conditions showed trans-complementation by the chromosomally located regulator gene product . These results confirmed the positive control model for amidase gene expression . Levels of amidase expression seen during these studies were approximately threefold higher than in the parental, amidase-positive strains.

Pathol Biol (Paris), 1984 Dec, 32(10), 1037 - 9
{Early detection of Pseudomonas aeruginosa in hemoculture media enriched with nitrates}; Boucaud-Maitre Y et al.; Addition of a small amount of nitrates in blood culture media enhances growth of Pseudomonas aeruginosa, and permits earliest detection of that bacteria even in anaerobes media.

Gan To Kagaku Ryoho, 1984 Dec, 11(12 Pt 2), 2674 - 80
{Biological activities of a new antitumor antibiotics}; Umezawa I; The antitumor antibiotic sporamycin is composed of polypeptide and non-chromophore subunits and shows remarkable antitumor activity against various animal tumors . The mechanism of action of this compound involves host-mediated antitumor activity as well as direct cytotoxic activity due to the inhibition of nucleic acid synthesis . Pretreatment of mice with sporamycin produced not only a remarkable inhibition of tumor growth but also strengthened the resistance of the host to infection with Pseudomonas aeruginosa . The immunological activity described above was also observed using the isolated polypeptide moiety of sporamycin . The antitumor antibiotic stubomycin possesses a marked cytotoxic activity against mammalian cells in vitro and in vivo . Stubomycin showed inhibitory activity against DNA, RNA and protein synthesis to almost the same degree . It was also shown that these activities were significantly reduced by lipids such as phosphatidylserine, olive oil and cardiolipin . On the other hand, stubomycin did not show any mutagenic effects in mammalian cells or bacteria . It seems that the primary action of stubomycin is due to change and ultimate lysis of the cell surface . It was observed that a new antibiotic, kazusamycin, possessed very strong cytotoxic activity against mammalian cells in vitro . However this compound exhibited no antibacterial activity against gram-positive and gram-negative bacteria . We are presently investigating the biological activities of a monoclonal antibody combined with kazusamycin.

J Leukoc Biol, 1984 Dec, 36(6), 771 - 4
Inhibition of yeast phagocytosis in macrophage cultures treated with slime polysaccharide purified from Pseudomonas aeruginosa; Grasso RJ et al.; This study was initiated to determine whether purified slime polysaccharide(PSP) from P aeruginosa inhibits the ingestion of heat killed Saccharomyces cerevisiae particles in macrophage cultures . Relative to controls, direct phagocytosis assays revealed that the percentages of phagocytes and the numbers of ingested yeast particles per phagocyte decreased in a dose-dependent manner in PSP-treated cultures . Thus, PSP may act as a virulence factor in vivo by impairing the phagocytic capacity of macrophages.

J Leukoc Biol, 1984 Dec, 36(6), 689 - 701
Opsonin-independent phagocytosis of surface-adherent bacteria by human alveolar macrophages; Lee DA et al.; Opsonin-independent mechanisms of phagocytosis may be important in host defense of certain body sites such as the lung . In this study, one such mechanism, "surface phagocytosis," was investigated by measuring the uptake of unopsonized {3H}-labeled Staphylococcus aureus and Pseudomonas aeruginosa adherent to a plastic surface by human alveolar macrophages (AM) and peripheral blood polymorphonuclear leukocytes (PMN) . Efficient uptake of unopsonized bacteria by both cell types was observed . Electron microscopic studies suggested that the manner in which these cell types encounter adherent bacteria is different . While AM appear to gather in organisms at their periphery as they spread out upon the underlying substrate, PMN seem to sweep bacteria up as they move along the plastic surface . Bacterial killing determined by a fluorochrome microassay was decreased by AM compared to PMN . Although the precise mechanism whereby phagocytes recognize unopsonized bacteria adherent to a surface remains to be determined, this aspect of phagocytic cell function may prove to have clinical relevance.

J Infect Dis, 1984 Dec, 150(6), 808 - 16
Epidemiology of endemic Pseudomonas aeruginosa: why infection control efforts have failed; Olson B et al.; The epidemiology of Pseudomonas aeruginosa was evaluated in an intensive care unit for a period of six months by means of serial surveillance and environmental cultures . One hundred (37%) of 270 patients were noted to be colonized: 63 at the time of their admission and 37 during their stay on the unit . Colonization at the time of admission was associated with length of hospitalization before admission to the intensive care unit, age, gastrointestinal disease, and prior use of antibiotics . The strains acquired on the intensive care unit represented several different serotypes, with little clustering; the source of most strains was not found . In only 12 cases did the acquisition of P . aeruginosa appear to represent cross-infection; the use of barrier isolation could have prevented at most five of these cases . Undetected endogenous gastrointestinal carriage may have been responsible for many other apparent acquisitions . Clinical infection in association with preceding gastrointestinal colonization developed in 20 patients . The data indicate that traditional control measures aimed at the prevention of exogenous acquisition of P . aeruginosa are unlikely to have an impact on the overall incidence of infection and that efforts to prevent infection in patients who are already colonized are necessary.

J Bacteriol, 1984 Dec, 160(3), 928 - 34
Pseudomonas aeruginosa mutants affected in anaerobic growth on arginine: evidence for a four-gene cluster encoding the arginine deiminase pathway; Vander Wauven C et al.; Pseudomonas aeruginosa PAO was able to grow in the absence of exogenous terminal electron acceptors, provided that the medium contained 30 to 40 mM L-arginine and 0.4% yeast extract . Under strictly anaerobic conditions (O2 at less than 1 ppm), growth could be measured as an increase in protein and proceeded in a non-exponential way; arginine was largely converted to ornithine but not entirely consumed at the end of growth . In the GasPak anaerobic jar (Becton Dickinson and Co.), the wild-type strain PAO1 grew on arginine-yeast extract medium in 3 to 5 days; mutants could be isolated that were unable to grow under these conditions . All mutants (except one) were defective in at least one of the three enzymes of the arginine deiminase pathway (arcA, arcB, and arcC mutants) or in a novel function that might be involved in anaerobic arginine uptake (arcD mutants) . The mutations arcA (arginine deiminase), arcB (catabolic ornithine carbamoyltransferase), arcC (carbamate kinase), and arcD were highly cotransducible and mapped in the 17-min chromosome region . Some mutations in the arc cluster led to low, noninducible levels of all three arginine deiminase pathway enzymes and thus may affect control elements required for induction of the postulated arc operon . Two fluorescent pseudomonads (P . putida and P . fluorescens) and P . mendocina, as well as one PAO mutant, possessed an inducible arginine deiminase pathway and yet were unable to grow fermentatively on arginine . The ability to use arginine-derived ATP for growth may provide P . aeruginosa with a selective advantage when oxygen and nitrate are scarce.

J Clin Hosp Pharm, 1984 Dec, 9(4), 303 - 9
Serum and sputum concentrations of azlocillin, cefoperazone and ceftazidime in patients with cystic fibrosis; Martini N et al.; Single-dose pharmacokinetics of azlocillin, cefoperazone and ceftazidime were studied in 17 patients with cystic fibrosis (CF) . All patients had broncho-pulmonary infections caused by Pseudomonas aeruginosa . Three groups of five, six, and six patients were treated with azlocillin, cefoperazone, or ceftazidime, respectively . The size of the single dose was 133 mg/kg for azlocillin, 66.7 mg/kg for ceftazidime and 66.7 mg/kg for cefoperazone . The clearance values for the three antibiotics calculated from the single-dose data were, on the average, higher than the values previously reported for normal subjects . After the first dose, the patients received a repeated-dose treatment with the same antibiotic . During the first 5 days of therapy, a complement postural drainage of sputum was obtained four times a day for each patient . Cefoperazone could be measured in 47 (39.2%) of the 120 sputum samples assayed while ceftazidime was shown to be present in all 120 sputum samples examined . Azlocillin was not detected in any of the 100 sputum samples assayed.

Biochem J, 1984 Dec 1, 224(2), 601 - 8
Electron-paramagnetic-resonance spectroscopy studies on the dissimilatory nitrate reductase from Pseudomonas aeruginosa; Godfrey C et al.; Preparations of nitrate reductase in the resting state from Pseudomonas aeruginosa exhibit an Mo(V) e.p.r . signal . Progressive reduction of the enzyme results at first in the intensification and then in the disappearance of the signal . Three different species of Mo(V) were detected by e.p.r . These are the high-pH species (g1 = 1.9871; g2 = 1.9795; g3 = 1.9632) and nitrate and nitrite complexes of a low-pH species (respectively g1 = 2.0004; g2 = 1.9858; g3 = 1.9670; and g1 = 1.9975; g2 = 1.9848; g3 = 1.9652) . These signals are closely analogous to those for the enzyme from Escherichia coli described by Vincent & Bray {(1978) Biochem . J . 171, 639-647} . Signals typical of iron-sulphur clusters were also detected . In the oxidized enzyme these are believed to arise from a {3Fe-4S} cluster (g = 2.01) and in the reduced enzyme from an unusual low-potential {4Fe-4S}+ cluster (g1 = 2.054; g2 = 1.952; g3 = 1.878) . The iron-sulphur centres were also studied in a 'high-catalytic-activity' form of the enzyme . Reduction with Na2S2O4 resulted in the formation of a complex signal with g values at 2.054, 1.952, 1.928, 1.903 and 1.878 . The signal could be deconvoluted by reductive titration of the enzyme into two species (g1 = 2.054; g2 = 1.952; g3 = 1.878; and g1 = 2.036; g2 = 1.928; g3 = 1.903) . The degradation of a {4Fe-4S} into a {3Fe-4S} cluster in the enzyme is suggested by these studies, the process being dependent on the method used to purify the enzyme . The addition of nitrate to the reduced enzyme results in the oxidation of Mo(IV) to Mo(V) and of all the iron-sulphur centres.

J Hosp Infect, 1984 Dec, 5(4), 371 - 6
Pseudomonas aeruginosa cross-infection following endoscopic retrograde cholangiopancreatography; Cryan EM et al.; In a 6 week period, three of 50 patients developed Pseudomonas aeruginosa septicaemia following Endoscopic Retrograde Cholangiopancreatography (ERCP) . Pseudomonas aeruginosa serotype 10 was isolated from each of the patients and from the endoscope . The outbreak was related to inadequate disinfection of the air and water channel of the endoscope . Following the introduction of a modified decontamination technique, which involved rinsing the air and water channel with glutaraldehyde, no further cases of pseudomonas infection occurred, and the organism could not be isolated from the instrument . Obstruction of the biliary tract was a predisposing factor in the development of infection; and administration of antibiotics immediately following the procedure failed to prevent it . This may have been due to inadequate dosage . We suggest that patients presenting for ERCP, in whom obstruction of the biliary tract is suspected, should come prepared for immediate drainage of the obstructed system at the time of the procedure.

J Hosp Infect, 1984 Dec, 5 Suppl A, 69 - 73
Experimental infection and hydrogel dressings; Leaper DJ et al.; The prolonged use of a hydrogel (polyacrylamide) dressing on circular 1 cm skin defects was tested in a rat experimental model . The rate of healing and changes in bacterial content following inoculation of 1 X 10(8) Staphylococcus aureus, Escherichia coli or Pseudomonas aeruginosa were measured . Wounds inoculated with Staph . aureus or E . coli prior to polyacrylamide occlusion did not have delayed wound contraction and healing and numbers of organisms were falling at 10 days . Wounds inoculated with Ps . aeruginosa showed a delay in healing with a large increase in organisms (greater than 1 X 10(10} after 10 days occlusion . Prolonged wound occlusion by hydrogel dressings may aid in healing by secondary intention but the presence or growth of pseudomonas indicates that frequent changes of dressings should be made.

Eur J Biochem, 1984 Nov 2, 144(3), 607 - 12
Phosphate transport in Pseudomonas aeruginosa . Involvement of a periplasmic phosphate-binding protein; Poole K et al.; A binding protein for inorganic phosphate was purified to apparent homogeneity from the shock fluids of phosphate-limited Pseudomonas aeruginosa . The purified protein bound one molecule of phosphate per molecule of binding protein with an average Kd of 0.34 microM . Arsenate, pyrophosphate and polyphosphates up to 15 units long could inhibit the binding of phosphate to the binding protein, although organic phosphates, such as glucose 6-phosphate, glycerol 3-phosphate and adenosine 5'-monophosphate could not . Mutants lacking the phosphate-binding protein were isolated and shown to be deficient in phosphate transport compared with wild-type cells . Two kinetically distinct systems for phosphate uptake could be observed in wild-type cells, with apparent Km values of 0.46 +/- 0.10 microM (high affinity) and 12.0 +/- 1.6 microM (low affinity) . In contrast, only a single low-affinity transport system was observable in mutants lacking the binding protein (Km apparent = 19.3 +/- 1.4 microM Pi), suggesting the involvement of the binding protein in the inducible high-affinity phosphate-uptake system of P . aeruginosa.

J Antimicrob Chemother, 1984 Nov, 14(5), 553 - 6
Interaction of clindamycin and cefpimizole (U63196E) in vitro against aerobic gram-negative rods and aerobic gram-positive cocci; Welch WD et al.; The combination of clindamycin plus a new semisynthetic cephalosporin, U63196E for which the United States approved name is cefpimizole, was tested against 47 aerobic Gram-negative rods and 30 aerobic Gram-positive cocci . Synergy was seen with Klebsiella pneumoniae (3 of 19 isolates) and Escherichia coli (2 of 21 isolates) . All isolates of Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant Staph . aureus, and enterococci demonstrated either indifference or antagonistic reactions to the drug combination.

J Antibiot (Tokyo), 1984 Nov, 37(11), 1456 - 61
Inhibition of fatty acid synthesis by the antibiotic thiolactomycin; Hayashi T et al.; The antibiotic thiolactomycin inhibits the growth of Escherichia coli K-12 and Pseudomonas aeruginosa 507 (beta-lactam supersensitive mutant) . A micrograph of E . coli cells, which were grown at a sublethal concentration of thiolactomycin (20 micrograms/ml), revealed the morphological change with cell elongation . The effects of the antibiotic on syntheses of cellular constituents were studied by measuring the incorporation of labeled precursors into lipids and macromolecules . This antibiotic preferentially inhibited the incorporation of {14C}acetate into fatty acids and lipids . Addition of both palmitate and oleate, but not of either fatty acid alone, reversed the growth inhibition of P . aeruginosa by thiolactomycin . These findings support the conclusion that the effects of thiolactomycin are due to a specific inhibition of fatty acid synthetase.

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