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