Behring Inst Mitt, 1984 Nov, (76), 113 - 20 A new polyvalent pseudomonas vaccine; Merle P et al.; A new polyvalent Pseudomonas aeruginosa vaccine consisting of extracts of the 24 serotypes of the Lanyi typing scheme was developed and evaluated in mouse protection studies . The vaccine, mainly consisting of lipopolysaccharides and outer membrane proteins was protective in passive and active protection studies . A rabbit antiserum against the vaccine showed high protective capacity in the IgG-fraction and was protective against 3 out of 6 challenge strains in a leucopenic mouse model. Acta Paediatr Scand, 1984 Nov, 73(6), 772 - 7 Relation between antibody response to Pseudomonas aeruginosa exoproteins and colonization/infection in patients with cystic fibrosis; Granstrom M et al.; Enzyme-linked immunosorbent assay (ELISA) was used to measure the antibody response to Pseudomonas aeruginosa exotoxin A, elastase, alkaline protease and phospholipase C in patients with cystic fibrosis (CF) . Only the chronically colonized patients showed elevated antibody titres to phospholipase C (22/22 patients), alkaline protease (16/22 patients), exotoxin A (15/22 patients) and elastase (5/22 patients) . In a few patients where serial specimens were available, rising titres were recorded to all four antigens during periods of active infection . Antibiotic treatment resulted in decrease of titres against all four antigens, but only the anti-exotoxin A and anti-elastase titres decreased to normal levels . Titres to phospholipase C were the least influenced by antibiotic treatment . The results imply different roles for these exoproteins in chronic colonization versus active infection . The levels of P . aeruginosa antibodies to exoproteins could probably be used in monitoring treatment of patients with CF. Zh Mikrobiol Epidemiol Immunobiol, 1984 Nov, (11), 26 - 33 {A nutrient medium for detecting the metallic luster of Pseudomonas aeruginosa colonies}; Kalina GP; Almost 100% of P . aeruginosa strains, when inoculated in macrocolonies (plaques), show metallic (golden) luster of their colonies grown on the medium containing 2,3,5-triphenyltetrazolium chloride, milk and a higher concentration of peptone; such luster, though less intensive, can also be observed in nonpigmented strains . This phenomenon can be used in the diagnosis of P . aeruginosa infections as a decisive sign. Antimicrob Agents Chemother, 1984 Nov, 26(5), 789 - 91 Synergistic activities of combinations of beta-lactams, fosfomycin, and tobramycin against Pseudomonas aeruginosa; Takahashi K et al.; The effects of antibiotic combinations against Pseudomonas aeruginosa infections frequently found in hospitalized patients were investigated . By means of an agar plate dilution checkerboard method, combinations of piperacillin-fosfomycin, cefoperazone-fosfomycin, and cefsulodin-fosfomycin were synergistic against 80.0, 85.0, and 82.6% of the strains tested . The mean fractional inhibitory concentration indices of piperacillin-fosfomycin, cefoperazone-fosfomycin, and cefsulodin-fosfomycin were 0.48, 0.42, and 0.46, respectively . The synergistic activities of these combinations were enhanced by the addition of a small amount of tobramycin, 0.25 micrograms/ml. Antimicrob Agents Chemother, 1984 Nov, 26(5), 678 - 82 Postantibiotic effect of imipenem on Pseudomonas aeruginosa; Bustamante CI et al.; Imipenem (formerly N-formimidoyl thienamycin) and ceftazidime were investigated for their postantibiotic effect on Pseudomonas aeruginosa . Four strains of P . aeruginosa in the logarithmic phase of growth were exposed for 1 and 2 h to concentrations of antibiotics achievable in human serum . Recovery periods of test cultures were evaluated after dilution or addition of beta-lactamase . A consistent postantibiotic effect against all strains was obtained with imipenem but not with ceftazidime . Although ceftazidime did not have a postantibiotic effect, it did suppress the growth of the organisms at concentrations equivalent to one-third of the MIC . The clinical implications of these effects need further evaluation. J Clin Microbiol, 1984 Nov, 20(5), 988 - 9 Interpretive standards and quality control guidelines for imipenem susceptibility tests with 10-micrograms disks; Barry AL et al.; Tests with 10-micrograms imipenem disks accurately categorized 98.5% of 551 bacterial isolates when interpretive breakpoints of less than or equal to 13 mm for resistant and greater than or equal to 16 mm for susceptible were used . Because a sufficient number of resistant or moderately susceptible strains were not available for testing, these interpretive standards must be considered tentative . Quality control limits for tests with Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 are 26 to 32 and 20 to 28 mm, respectively . Zones obtained with Staphylococcus aureus ATCC 25923 were too large and variable to be useful for quality control purposes. J Clin Microbiol, 1984 Nov, 20(5), 855 - 9 Production of leukocidin by clinical isolates of Pseudomonas aeruginosa and antileukocidin antibody from sera of patients with diffuse panbronchiolitis; Homma JY et al.; The ratio of leukocidin-producing strains to clinical isolates of Pseudomonas aeruginosa was investigated together with the production of protease, elastase, and exotoxin A . We also examined whether these strains contain the common antigen which resides in the cell wall . By using the agar gel diffusion test with specific antisera, we found that 87 of 90 (96.7%) of clinical isolates produced leukocidin . Protease, elastase, and exotoxin A were also produced at high percentages . The common antigen was found to exist in all strains . Next, to estimate antileukocidin antibody in the sera of patients, we used an enzyme-linked immunosorbent assay with horseradish peroxidase-protein A . The sera of 39 patients with diffuse panbronchiolitis (DPB) were investigated for antileukocidin antibody . The mean antileukocidin titer in the sera of 17 DPB patients who were not infected with P . aeruginosa and 5 DPB patients who were transiently infected with the bacteria was about the same as the mean antileukocidin titer in the sera of 11 healthy controls, whereas the mean antileukocidin titer in the sera of 17 DPB patients who were persistently colonized was significantly higher than that in healthy controls . These results indicate that leukocidin was produced at the local site of infection in DPB patients. Biochem J, 1984 Nov 1, 223(3), 921 - 4 Quinoprotein alcohol dehydrogenase from ethanol-grown Pseudomonas aeruginosa; Groen B et al.; Cell-free extracts of Pseudomonas aeruginosa strains, grown on ethanol, showed dye-linked alcohol dehydrogenase activities . The enzyme responsible for this activity was purified to homogeneity . It appeared to contain two molecules of pyrroloquinoline quinone per enzyme molecule . In many respects, it resembled other quinoprotein alcohol dehydrogenases (EC 1.1.99.8), having a substrate specificity intermediate between that of methanol dehydrogenases and ethanol dehydrogenases in this group . On the other hand, it also showed dissimilarities: the enzyme was found to be a monomer (Mr 101 000), to need only one molecule of the suicide substrate cyclopropanol to become fully inactivated, and to have a different aromatic amino acid composition. Am J Ophthalmol, 1984 Nov, 98(5), 548 - 51 Bacterial contamination of eyedrop dispensers; Coad CT et al.; We undertook an in vitro investigation of the role of the design of the eyedrop dispenser in bacterial contamination . The nozzle tips of pipette and squeeze bottles containing Fluress (pH 5.0) were inoculated with 10 microliter of an ocular isolate of Pseudomonas aeruginosa (5.5 X 10(5) bacteria/ml) . Cultures of single drops of ophthalmic solution (25-microliter drops from each pipette bottle and 40-microliter drops from each squeeze bottle) were done one minute, 15 minutes, one hour, two hours, and 24 hours after inoculation . Swabs from the inside of the caps of the eyedrop bottles were also cultured at similar intervals . No bacteria were recovered from either dispenser type after one hour . Swabbings from the caps of the pipette bottles showed no growth within minutes after inoculation, but swabbings from the caps of the squeeze bottles consistently yielded bacteria for 24 hours . We suggest that the cap of the squeeze bottle serves as a potential reservoir for bacterial contamination whereas direct contact of microorganisms with the preservative in an ophthalmic solution by the use of a pipette-type dispenser decreases the risk of microbial contamination and growth. J Oral Maxillofac Surg, 1984 Nov, 42(11), 699 - 704 The effects of antibiotic-supplemented bone allografts on contaminated, partially avulsive fractures of the canine ulna; Petri WH 3rd et al.; The use of antibiotic-supplemented bone allograft as a material for placement in contaminated fractures of the dog ulna was investigated . Demineralized, freeze-dried bone allografts mixed with antibiotics and gelatin were placed in five fractures contaminated with Staphylococcus aureus (Washington Hospital strain) and Pseudomonas aeruginosa (PA 220) . The results of treatment with antibiotic-supplemented bone allografts were compared with the results of conventional treatment in five additional experimental animals in which fractures contaminated with S . aureus and P . aeruginosa were created . The five fractures treated by conventional methods developed acute osteomyelitis and nonunion, whereas the ASBA-treated fractures resulted in bone union without infection . ASBA-treated fractures were stable and had 89% of the shearing strength of the non-fractured, contralateral ulnae five months after treatment. Cancer Res, 1984 Nov, 44(11), 4919 - 23 Effect of malignant transformation, retinoic acid, trifluoperazine, and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) on the sensitivity of rodent cells to Pseudomonas toxin; Sundan A et al.; A number of mouse and rat cells and their virus-transformed counterparts were tested for sensitivity to Pseudomonas aeruginosa exotoxin A (PEA) . In each case, the transformed cells were considerably less sensitive than were the nontransformed cells . In the presence of trifluoperazine, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, or retinoic acid, the transformed cells became as sensitive as the nontransformed cells, whereas these drugs had little or no effect on the sensitivity to PEA of the nontransformed cells . Temperature-sensitive virus-transformed normal rabbit kidney cells were sensitized to PEA by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, when these cells were grown as the transformed phenotype, whereas the nontransformed phenotype could not be sensitized . The possibility is discussed that upon malignant transformation a process which is dependent upon calmodulin or protein kinase C strongly decreases the sensitivity of the cells to PEA. J Exp Med, 1984 Nov 1, 160(5), 1338 - 49 Identification of the principal T lymphocyte-stimulating antigens of Pseudomonas aeruginosa; Parmely MJ et al.; To aid in understanding the role of cellular immunity in limiting Pseudomonas aeruginosa infections, we have identified some of the principal antigens of the organism that are recognized by human T cells . Clones of T cells were selected in such a manner that they would provide information not only about the identity of Pseudomonas antigens, but also the T cell repertoires of immune donors . Most clones were found to be specific for Pseudomonas alkaline protease (AP) . Such clones could be physically isolated by selecting with crude Pseudomonas antigens or purified AP . In either case, their fine specificities were the same when tested against a panel of Pseudomonas antigens . The conclusion that AP is the principal immunogen for many donors was confirmed by measuring the absolute frequencies of proliferating T cells committed to AP and all other Pseudomonas antigens . Frequencies of AP-specific clones (1.5-2.7 X 10(-5} were comparable to those from the same donors that were specific for all secreted Pseudomonas antigens (1.3-6.0 X 10(-5} . These results provide a model system for studying human T cell-mediated immunity to bacteria by identifying discrete antigens and measuring the repertoire diversities of cells responding to them. Arch Microbiol, 1984 Nov, 140(1), 40 - 3 Mutants of Pseudomonas aeruginosa unable to inactivate allantoinase and NADP-dependent glutamate dehydrogenase; Smits RA et al.; Both allantoinase and NADP-GDH in Pseudomonas aeruginosa were inactivated when cells reached the stationary phase of growth . Mutants unable to inactivate these enzymes were isolated . Results with recombinants showed that the mutation is not located in the structural genes of these enzymes but in an independent gene involved in the inactivation. Plasmid, 1984 Nov, 12(3), 170 - 80 Insertion mutations in the promiscuous IncP-1 plasmid R18 which affect its host range between Pseudomonas species; Krishnapillai V et al.; Fifty-one host range mutants of the promiscuous plasmid R18 were isolated by Tn7 insertion mutagenesis by using Pseudomonas aeruginosa as the permissive, and P . stutzeri as the nonpermissive, host . Endonuclease cleavage mapping of 40/51 mutants showed that 37 mutations mapped to kilobase coordinates 40.3-43.8 in the two overlapping genes encoding plasmid DNA primase . Thus by this procedure it has been possible readily to isolate a large number of primase mutants . The majority of these mutations mapped to the overlapping DNA whereas a few also mapped to the nonoverlap region encoding the larger 118-kDa polypeptide . Among these mutants were four which had long deletions within the overlapping segment and extending to varying lengths anticlockwise of it . The genetic defect in these mutants has been correlated with greatly reduced in vitro primase enzyme activity . The primase mutations drastically affected the mutant's ability to mobilize a nonconjugative, wide-host-range IncP-4(Q) plasmid from P . aeruginosa to P . stutzeri although mobilization within P . aeruginosa was affected to a lesser degree . Other insertion mutations were mapped to the regions of plasmid origin of transfer (oriT) and origin of replication (oriV), but their physical location was different to previously identified similar mutations obtained using Escherichia coli as the nonpermissive host . Their physically distinct locations were correlated with differences in their transmissibility from P . aeruginosa into enteric bacterial species and into other Pseudomonas species. J Clin Microbiol, 1984 Nov, 20(5), 1020 - 1 Simple method for collagenase determination in 38 Pseudomonas aeruginosa strains; Wellisch G et al.; Collagenase enzyme activity of 38 Pseudomonas aeruginosa strains and 38 strains of Escherichia coli from various pathological sources was measured by a simple method . This method uses plates with collagen gel . The rate of gel lysis is proportional to the collagenase concentration . The method is simple and requires no special materials or equipment . From the 38 P . aeruginosa strains, 34 were collagenase positive . All 38 strains of E . coli were collagenase negative. J Antimicrob Chemother, 1984 Nov, 14(5), 491 - 7 The serum bactericidal activity of latamoxef (moxalactam), cefoperazone and cefotaxime; McNamee W et al.; We determined the serum bactericidal activity 1 h after the end of 2 g, 30 min infusions of latamoxef, cefoperazone and cefotaxime in six volunteers against six strains each of Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Pseudomonas aeruginosa . All produced excellent serum bactericidal activity against E . coli . Latamoxef and cefotaxime were superior for K . pneumoniae . Cefoperazone produced the highest titres against Staph . aureus . None of these agents produced sufficient bactericidal activity against Ps . aeruginosa to be useful in initial single agent therapy for the septic, granulocytopenic cancer patient. J Biol Chem, 1984 Oct 25, 259(20), 12403 - 8 The reaction between NADPH and mercuric reductase from Pseudomonas aeruginosa; Sahlman L et al.; The reaction between the FAD-containing enzyme, mercuric reductase, and its reducing substrate, NADPH, has been studied at 5 degrees C, pH 7.3, by rapid-scan and fixed-wavelength stopped-flow techniques with the aim to characterize reaction intermediates . With an excess of NADPH the spectral changes observed in rapid-scan experiments can be described by a simple kinetic model, A----B----C----D, where A, B, C, and D represent distinct spectral species . The first step is virtually complete within the dead time of the apparatus . It is associated with a 16% bleaching of flavin absorbance and the appearance of a very broad charge-transfer band (epsilon max = 1.9 mM-1 cm-1) centered near 600 nm . The second step (k = 43 s-1) involves a further small bleaching of flavin absorbance and intensification of the charge-transfer band (epsilon max = 3.3 mM-1 cm-1) which becomes centered near 580 nm . The third step (k = 8 s-1) involves an intensification and a blue shift of the main FAD absorption band . Concurrently, the charge-transfer band increases in intensity and becomes centered near 530 nm (epsilon 530 = 5.0 mM-1 cm-1) . While the first two steps involve 1 mol of NADPH per mol of FAD, the third step requires a second equivalent of NADPH . A 2-electron-reduced enzyme (EH2) can be obtained by treatment of the oxidized enzyme (E) with dithioerythritol . Addition of 1 eq of NADP+ to dithioerythritol-generated EH2 gives rise to a spectral species similar to the kinetic intermediate C, while the addition of 1 eq of NADPH gives rise to a spectral species similar to D . It is proposed that B largely corresponds to an E-NADPH complex, C to an EH2-NADP+ complex, and D to an EH2-NADPH complex. Biochem J, 1984 Oct 15, 223(2), 379 - 91 The nature of species prepared by photolysis of half-reduced, fully reduced and fully reduced carbonmonoxy-cytochrome c-551 peroxidase from Pseudomonas aeruginosa; Greenwood C et al.; The half-reduced, fully reduced and fully reduced CO-bound forms of the enzyme cytochrome c-551 peroxidase isolated from Pseudomonas aeruginosa were examined by a combination of low-temperature absorption and magnetic-circular-dichroism spectroscopy . Deliberate low-temperature (4.2K) photolysis of these forms of the enzyme, in all of which the high-potential haem is in the ferrous state, revealed that this haem group, assigned to have a histidine-methionine ligand set, is photosensitive . The photolabile ligand is most likely to be the methionine residue, and the product of photolysis, namely the high-spin (S = 2) ferrous form, is stable at low temperature (4.2K) . Warming to approx . 20K allows thermal recombination to occur, restoring the low-spin (S = 0) state . The low-potential haem (bis-histidine ligation) is photoinert in both ferric and ferrous states; however, the photosensitive CO adduct of this centre cannot be maintained as the photolysed (S = 2) product at 4.2K . This surprising observation may be due to quantum-mechanical tunnelling of the CO through the activation barrier even at 4.2K, implying that the activation barrier to thermal recombination is both narrow and low . Low-temperature absorption spectroscopy reveals that the high-potential haem has a very characteristic low-spin ferrous spectrum with intense highly structured beta- and split alpha-bands, whereas the spectrum of the low-potential ferrous haem contains alpha- and beta-bands devoid of fine structure. Biochem J, 1984 Oct 15, 223(2), 369 - 78 A study of the oxidized form of Pseudomonas aeruginosa cytochrome c-551 peroxidase with the use of magnetic circular dichroism; Foote N et al.; The magnetic properties at different temperatures of oxidized Pseudomonas aeruginosa cytochrome c-551 peroxidase were studied, with the use of the technique of magnetic-circular-dichroism spectroscopy . At 4.2K, both constituent haems were found to be low-spin, and the axial ligand pairs were identified as histidine-histidine and histidine-methionine . At room temperature high-spin signals were observed, amounting to less than 25% of the total haem present . These signals are concluded to arise mainly from a temperature-dependent spin-state equilibrium in the methionine-ligated haem. Biochemistry, 1984 Oct 9, 23(21), 5076 - 80 Antibody inhibition of ferripyochelin binding to Pseudomonas aeruginosa cell envelopes; Sokol PA et al.; A 14K molecular weight protein which has been shown to bind ferripyochelin has been purified from cell envelopes of Pseudomonas aeruginosa low iron grown cells . The purified protein migrated as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was shown to be free of contamination by lipopolysaccharide or carbohydrate . Antiserum to this protein was made in rabbits and was shown to react with the purified protein by immunoblot assay . The immunoglobulin G fraction of this antiserum blocked binding of {59Fe}pyochelin to isolated cell envelopes of P . aeruginosa in a dose-dependent fashion. Proc Natl Acad Sci U S A, 1984 Oct, 81(20), 6554 - 8 Preparation and characterization of pentaammineruthenium-(histidine-83)azurin: thermodynamics of intramolecular electron transfer from ruthenium to copper; Margalit R et al.; The reaction between a5RuH2O2+ (a is NH3) and Pseudomonas aeruginosa azurin at pH 7, followed by oxidation, yields a5Ru(His-83)3+-azurin(Cu2+) as the major product . Spectroscopic measurements (UV-visible, CD, EPR, and resonance Raman) indicate that the native structure is maintained in the modified protein . The site of ruthenium binding (His-83) was identified by peptide mapping . The a5RuHis/Cu ratio in the modified protein, determined from the EPR spectrum, is 1:1, and the reduction potentials (vs . normal hydrogen electrode, pH 7.0, 25 degrees C) are blue copper (Cu2+/1+), 320 +/- 2 mV; a5Ru(His-83)3+/2+, 50 +/- 10 mV . From measurements of the reduction potentials at several temperatures in the 5-40 degrees C range, delta H degree for intramolecular Ru2+ ----Cu2+ electron transfer was estimated to be -12.4 kcal mol-1 (1 cal = 4.184 J) . Analysis of kinetic data in light of the electron transfer exothermicity indicates that the reorganizational enthalpy of the blue copper site can be no larger than 7.1 kcal mol-1. J Otolaryngol, 1984 Oct, 13(5), 289 - 95 Clinical and microbiological features of otitis externa; Hawke M et al.; A prospective study of 40 cases of acute otitis externa and 99 cases of chronic otitis externa in unselected patients revealed that otitis externa affects males and females with a similar frequency . The peak incidence occurs in the summer and early fall months of the year . Exposure to water, previous use of ear drops, and cotton-tipped applicators predisposed to both acute and chronic otitis externa . Hearing aid ear molds appear to be a predisposing factor in the development of chronic otitis externa . Pain, itching, discharge, and hearing loss were the most common presenting complaints in both acute and chronic otitis externa . The discharge in chronic otitis externa is more commonly purulent, whereas in acute otitis externa it is more commonly mucoid . The tympanic membrane is not frequently involved in acute otitis externa; however, in chronic otitis externa changes in the tympanic membrane were more often encountered . Most infections were of a pure bacterial origin, primarily Pseudomonas aeruginosa and Staphylococcus aureus . Fungi were the causative organisms more commonly in chronic otitis externa than in acute otitis externa (Figure 7) . It was found that previous usage of ear drops was more often associated with otomycosis in acute otitis externa and yet was not related to a higher frequency of otomycosis in chronic otitis externa . The presence of a foreign material, such as an ear mold, was associated with a greater frequency of mixed infections (bacteria and fungi) in the group with chronic otitis externa . The presence of a greenish discharge or foul odor was not related to any particular organism. Antimicrob Agents Chemother, 1984 Oct, 26(4), 597 - 8 In vitro activity of ciprofloxacin against aerobic gram-negative bacteria; Rudin JE et al.; For 177 gram-negative isolates, the MICs for ciprofloxacin ranged from 0.02 microgram/ml (Escherichia coli) to 0.31 microgram/ml (Pseudomonas aeruginosa) . In time-kill curves, ciprofloxacin at 8 X the MIC almost completely killed 10(6) CFU of P . aeruginosa by 24 h . Ciprofloxacin at 4 X the MIC allowed bacterial regrowth by 24 h, with development of partial resistance to ciprofloxacin. Antimicrob Agents Chemother, 1984 Oct, 26(4), 575 - 7 Addition of rifampin to carboxypenicillin-aminoglycoside combination for the treatment of Pseudomonas aeruginosa infection: clinical experience with four patients; Yu VL et al.; Four patients infected with Pseudomonas aeruginosa were treated with the triple therapy of carboxypenicillin (carbenicillin or ticarcillin), aminoglycoside (gentamicin or tobramycin), and rifampin . Two patients had P . aeruginosa endocarditis, one had bacteremia associated with granulocytopenia, and one had neurosurgical meningitis . In all four cases, the clinical condition of the patient deteriorated on combined antipseudomonal penicillin and aminoglycoside therapy . All patients had persistent blood cultures (throughout a 3- to 30-day period) or cerebrospinal fluid cultures (throughout a 24-day period) while receiving penicillin-aminoglycoside therapy . Rifampin, 600 mg every 8 h orally, was added to the penicillin-aminoglycoside regimen . All four patients defervesced within 24 h after the initiation of rifampin . In addition, all four patients experienced sterilization of blood and cerebrospinal fluid cultures within 24 h of therapy . The emergence of rifampin-resistant P . aeruginosa was not observed . Ultimately, two patients survived their infection; the other two patients succumbed to complications of their underlying disease . This clinical experience should provide a stimulus for a controlled evaluation of rifampin as a component of multiple drug therapy directed against P . aeruginosa. Arch Dermatol, 1984 Oct, 120(10), 1304 - 7 Recreationally associated Pseudomonas aeruginosa folliculitis . Report of an epidemic; Fox AB et al.; An epidemic of Pseudomonas aeruginosa folliculitis occurred in 117 persons . An indoor swimming pool at a dude ranch was the source of the infection . Recognition of the epidemic occurred through four patients who reported to our clinic with a characteristic syndrome of follicular pustular eruptions and associated symptoms . Inadequate disinfection of the water was causative . Many affected persons had prolonged contact with the organism because swimsuits were worn for several hours after exposure . Early diagnosis and epidemiological investigation are important in treating this disorder. J Am Coll Cardiol, 1984 Oct, 4(4), 680 - 4 Acute endocarditis in drug addicts: surgical treatment for multiple valve infection; Silverman NA et al.; In 72 drug abusers surgically treated for acute infective endocarditis, 14 patients (19%) required surgical procedures on two valves . The predominant infecting organisms were Staphylococcus aureus and Pseudomonas aeruginosa (29%) . In contrast to single valve infection, congestive heart failure was the most common operative indication (86%, p less than 0.05) and was uniformly present when both left-sided valves were involved . Surgery was performed 20 +/- 13 days after initiation of antibiotic therapy, yet 7 of the 14 patients had perivalvular abscess formation . In nine patients with solely left-sided infection, aortic and mitral valve replacements were performed . In five patients with bilateral infection, partial or complete tricuspid valvectomy was performed in conjunction with one aortic and four mitral valve replacements . Tricuspid valve competence was reestablished by valve insertion or anuloplasty in two patients, and these patients experienced less perioperative heart failure than did those with tricuspid excision alone . There was no early (less than 30 day) mortality . However, long-term follow-up revealed a reoperative incidence of 21% and a 36% late mortality rate due to prosthetic valve infection with or without dehiscence at 3 to 18 months (mean 7.2 +/- 6) after the initial operation . These late infectious complications were not related to infecting organism or prosthetic material in the tricuspid anulus, but did occur in four (57%) of seven patients with intracardiac abscess . The data indicate that multiple valve infection does not preclude successful early surgical therapy, maintaining tricuspid competence may be hemodynamically preferable, and reinfection in this addict population increases late mortality. Zh Mikrobiol Epidemiol Immunobiol, 1984 Oct, (10), 30 - 6 {Arginine medium for the isolation and primary identification of Pseudomonas aeruginosa in environmental objects}; Kalina GP; A culture medium for the isolation and primary identification of P . aeruginosa has been developed . The medium contains L-arginine and ions of K, Na, Mg, C and P; it has also an overlay of plain agar with 0.6% of 2,3,5-triphenyltetrazolium chloride added . The comparison of arginine medium with other media proposed for the isolation of P . aeruginosa from various objects in the environment has demonstrated the advantage of this highly selective medium permitting the primary identification of up to 95% of characteristic colonies. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1984 Oct, 258(1), 120 - 7 The synergism between cetrimide and antibiotics against Pseudomonas aeruginosa; el-Nima EI; Forty eight clinical isolates of P . aeruginosa were tested for susceptibility to seven different antimicrobial agents . When tested on Mueller-Hinton agar, the isolates were found to be resistant to ampicillin, sensitive to the antipseudomonal antibiotics, polymyxin B, gentamicin and carbenicillin . Polymyxin B inhibited all the isolates, whereas both carbenicillin and gentamicin inhibited 92.1% of the isolates . Neomycin, sulphamethoxypyridazine and chlortetracycline showed moderate activity and inhibited 50%, 28.9% and 15.8% of the isolates, respectively . However, on Mueller-Hinton agar supplemented with 0.03% cetrimide, the isolates succumbed readily to antimicrobial agents . In addition to polymyxin B, gentamicin and carbenicillin, all the strains were inhibited by neomycin and 94.7%, 92.1% and 63.6% of the isolates were inhibited by sulphamethoxypyridazine, chlortetracycline and ampicillin, respectively . Cetrimide, in concentrations ranging from 0.01 to 0.04% decreased the MIC of ampicillin against all the isolates, whereas 0.1% and 0.5% polysorbate 80 (tween 80) had no effect on the MIC . Growth inhibition studies have shown that the number of survivors was greatly reduced in presence of cetrimide and ampicillin . There was also an appreciable increase in the uptake of ampicillin by the bacterial cells in the presence of cetrimide. Antimicrob Agents Chemother, 1984 Oct, 26(4), 546 - 51 Use of the fluorescent probe 1-N-phenylnaphthylamine to study the interactions of aminoglycoside antibiotics with the outer membrane of Pseudomonas aeruginosa; Loh B et al.; The mode of interaction of the polycationic aminoglycoside antibiotics with the surface of Pseudomonas aeruginosa cells was studied with the hydrophobic fluorescent probe 1-N-phenylnaphthylamine (NPN) . The addition of the aminoglycoside gentamicin to intact cells in the presence of NPN led to a shift in the fluorescence emission maximum from 460 to 420 nm . At the same time the NPN fluorescence intensity increased fourfold . Gentamicin caused no such effects when added to outer membrane vesicles, suggesting that the increased fluorescence resulted from the interaction of gentamicin with intact cells . Gentamicin-promoted NPN uptake was inhibited by the divalent cations Mg2+ and Ca2+, but occurred in the absence of gentamicin transport across the inner membrane . Low concentrations of gentamicin (2 micrograms/ml) caused NPN fluorescence to increase over a period of 4 min in a sigmoidal fashion . At higher concentrations (50 micrograms/ml) the increase occurred within a few seconds . The final fluorescence intensity was almost independent of the gentamicin concentration . A centrifugation technique was used to demonstrate that gentamicin caused actual uptake of NPN from the supernatant . The initial rate of NPN uptake varied according to the gentamicin concentration in a sigmoidal fashion . Similar data were obtained for seven other aminoglycoside antibiotics . The data, when reanalyzed as a Hill plot, gave a series of lines with a mean slope (the Hill number) of 2.26 +/- 0.26, suggesting that the interaction of aminoglycosides with the cell surface to permeabilize it to NPN involved at least three sites and demonstrated positive cooperativity . There was a statistically significant relationship between the pseudoassociation constant K, from the Hill plots and the minimal inhibitory concentrations for the eight antibiotics . These results are consistent with the concept that aminoglycosides interact as a divalent cation binding site on the P . aeruginosa outer membrane and permeabilize it to the hydrophobic prove NPN. Antimicrob Agents Chemother, 1984 Oct, 26(4), 519 - 21 Effect of aztreonam in combination with azlocillin or piperacillin on Pseudomonas aeruginosa; Wu DH et al.; Aztreonam, a synthetic monobactam antimicrobial agent specifically active against aerobic, gram-negative microorganisms, was studied in combination with the extended-spectrum penicillins azlocillin and piperacillin against 46 strains of Pseudomonas aeruginosa . Of these strains, 4.3% were synergistically inhibited, and 19.7% showed evidence for an additive effect of the antibiotics . All other strains showed indifference . The addition of cefoxitin to these combinations increased the MICs of azlocillin and piperacillin by two to three tubes, whereas zero- to one-tube increases were noted for aztreonam MICs . Attempts to block cefoxitin-induced beta-lactamase production by using clindamycin were unsuccessful even at high clindamycin concentrations. Antimicrob Agents Chemother, 1984 Oct, 26(4), 485 - 8 Resistance of Pseudomonas aeruginosa to new beta-lactamase-resistant beta-lactams; Godfrey AJ et al.; An isogenic set of mutants of Pseudomonas aeruginosa, altered in permeability or permeability plus constitutive production of beta-lactamase, was examined for susceptibility to newer beta-lactam antibiotics . Kinetic data on the chromosomal beta-lactamase and susceptibility studies for the test beta-lactams indicate that permeability was the major mechanism of resistance to the poorly hydrolyzed and nonhydrolyzed antibiotics, e.g., carbenicillin, moxalactam, and cefsulodin . An exception was cefotaxime, with a low Km and a low Vmax, which had reduced efficacy in the permeability mutant and was further affected by the constitutive beta-lactamase . In this case, since the Vmax was low, a nonhydrolytic barrier may provide the additional reduction in susceptibility. Acta Pathol Microbiol Immunol Scand {C}, 1984 Oct, 92(5), 307 - 12 Detection of proteases of Pseudomonas aeruginosa in immune complexes isolated from sputum of cystic fibrosis patients; Doring G et al.; Sera and sputa of 12 cystic fibrosis patients suffering from chronic Pseudomonas aeruginosa lung infections were assayed for immune complexes using the Raji cell assay . Whereas all sera were negative, 33% of the sputa were positive for immune complexes . Sera and sputa of these patients were also assayed for antibodies against P.aeruginosa alkaline protease (AP) and elastase (Ela) and sputa for AP and Ela, using radioimmunoassays . All patients revealed antibody titers to the proteases in serum (1:5-1:1000) and eight patients had antibody titers to the proteases in sputum (1:5-1:100); all sputa were negative for AP and Ela . Sputum immune complexes and IgG were separated from whole sputum on a Protein A-Sepharose C1-4B column and treated with 0.75 M 2-mercaptoethanol and iodoacetamide after elution . After treatment, 58% of the sputa were positive for AP and/or Ela (5-200 ng/ml sputum) . The present study shows that proteases of P.aeruginosa are bound in immune complexes after the initiation of the immune response to these antigens and it yields new insights into the role of these proteases in chronic lung infection in cystic fibrosis. J Infect Dis, 1984 Oct, 150(4), 570 - 6 Protection against infection with Pseudomonas aeruginosa by passive transfer of monoclonal antibodies to lipopolysaccharides and outer membrane proteins; Sawada S et al.; Experimental infection with Pseudomonas aeruginosa was treated with eight different monoclonal antibodies (MCAs) produced by hybridoma cells obtained through cell fusion of mouse plasmacytoma cells and spleen cells from mice immunized with a virulent strain of P . aeruginosa (Homma serotype 7) . Five MCAs bound to lipopolysaccharides (LPSs) specific to serotype 7 or serotypes 2, 7, and 13, whereas the other three MCAs bound with broad specificities to outer membrane protein (OMP) fractions . The MCAs to LPS were highly protective against infection, with 50% protective doses of 0.05-2.5 micrograms of immunoglobulin per mouse . In contrast, the MCAs to OMP were much less protective, with a 50% protective dose range of 10 to greater than 100 micrograms of immunoglobulin per mouse . Most of the MCAs to LPS agglutinated P . aeruginosa cells, but all the MCAs to OMP produced so far have not, although all the MCAs bound well to the cells . Agglutinating MCAs provided better protection than did nonagglutinating MCAs. J Clin Microbiol, 1984 Oct, 20(4), 758 - 62 Association of infection caused by Pseudomonas aeruginosa serotype O11 with intravenous abuse of pentazocine mixed with tripelennamine; Levin MH et al.; From July 1979 to June 1983, 25 of 40 intravenous drug addicts with systemic infections had Pseudomonas aeruginosa as the etiological agent; by 1982, P . aeruginosa had replaced Staphylococcus aureus as the most common pathogen . At least 21 of the 25 addicts with P . aeruginosa infection abused pentazocine mixed with tripelennamine (commonly known as T's and blues) compared with 6 of 15 addicts infected with other pathogens (P = 0.006) . Of the 25 P . aeruginosa isolates, 23 were of serotype O11 . Phenotypic patterns in isolates from addicts and in 22 serotype O11 control isolates from nonaddicts were determined by pyocin and electrophoretic enzyme typing, as well as by susceptibility to heavy metals and antibiotics . Of 25 isolates from addicts, 20 were identical or differed by only one marker, whereas the 22 nonaddict serotype O11 isolates were distributed among 17 distinct phenotypic patterns . We postulate that the emergence of P . aeruginosa as the major cause of deep infection in addicts is a consequence of contamination of their paraphernalia during preparation of pentazocine and tripelennamine for self-injection . The phenotypic similarity among isolates from addicts may reflect acquisition from related environmental sources and an unusual ability of certain serotype O11 strains to survive preparation of the drugs or to be invasive. Drug Intell Clin Pharm, 1984 Oct, 18(10), 772 - 83 Antibiotic use in cystic fibrosis; Kelly HW et al.; Chronic pulmonary infections contribute significantly to the morbidity and mortality of patients with CF . The primary pathogens are Pseudomonas aeruginosa (PA) and Staphylococcus aureus . Hemophilus influenzae has been isolated from a significant number of patients also . A number of the beta-lactam and aminoglycoside antibiotics reportedly have altered pharmacokinetic variables in CF . Therapy of acute pulmonary deterioration consists of intravenous antibiotics for two weeks . Antibiotic selection is based on culture and sensitivity results . Currently, the combination of a broad-spectrum penicillin and an aminoglycoside seems to provide the best results . Prophylactic antibiotics are effective if the primary isolates are sensitive to the agents used . Chronic PA infections are problematic because effective oral agents are not available . Aerosolized antibiotics do not improve results over adequate systemic therapy for acute exacerbations . Questions regarding optimal dosages, frequency, and duration of therapy remain. Arch Dermatol, 1984 Oct, 120(10), 1337 - 40 Hot tub-associated dermatitis due to Pseudomonas aeruginosa . Case report and review of the literature; Chandrasekar PH et al.; A healthy, 27-year-old man had development of a maculopapular, pustular rash due to Pseudomonas aeruginosa, serotype 0:4, after bathing in a hot tub . Two persons sharing the same tub manifested a similar rash . In the first patient, the eruption was distributed mainly over the back, buttocks, and upper arms, appearing abruptly within 24 to 72 hours after use of the hot tub . Pruritus, malaise, and low-grade fever were the main associated features . The rash subsided spontaneously within ten days . This article reviews the literature on this form of cutaneous infection due to P aeruginosa. South Med J, 1984 Oct, 77(10), 1228 - 30 Pseudomonas aeruginosa causing osteomyelitis after puncture wounds of the foot; Graham BS et al.; Osteomyelitis of the foot caused by Pseudomonas aeruginosa has been a recognized complication of puncture wounds since 1968 . This is a report of two cases, one of which had evidence that the source of the P aeruginosa was the inner sole of the footwear . Factors such as warm, moist environment, antibiotics or antiseptics directed against gram-positive flora, and serous exudates, all of which enhance the growth of P aeruginosa, should be avoided in the management of puncture wounds of the foot. Antimicrob Agents Chemother, 1984 Oct, 26(4), 539 - 45 Evidence for two distinct mechanisms of resistance to polymyxin B in Pseudomonas aeruginosa; Moore RA et al.; Pseudomonas aeruginosa H181 and H185 are resistant to initial exposure to polymyxin B and continue to grow in its presence . Growth of the strains in the presence of 50 U of polymyxin B per ml was characterized by a doubling time of 120 min, whereas the doubling time in the absence of polymyxin was 60 min . Growth for two generations in the presence of polymyxin caused a 23 to 31% increase in lipopolysaccharide content . In addition, a marked increase in susceptibility to the detergents sodium deoxycholate, Triton X-100, and sodium dodecyl sulfate was observed . The resistant mutants had a small but significant reduction in their levels of dodecanoic acid as compared with the parent strain; however, this was the only consistent alteration observed in levels of fatty acids or readily extractable lipids . Polymyxin was fluorescently labeled by coupling to 1-dimethylaminonaphthalene-5-sulfonyl chloride (dansyl chloride) . Growth of strains H181 and H185 in the presence of dansylated polymyxin resulted in a stable association between the fluorescent antibiotic and the outer membrane . We postulate that these alterations are part of an adaptive response by the strains to the presence of polymyxin in the growth medium and reflect a resistance mechanism distinct from the mechanism affording polymyxin B resistance when these strains are initially exposed to the antibiotic. Genetika, 1984 Oct, 20(10), 1612 - 9 {Wide distribution of transposable phages in natural Pseudomonas aeruginosa populations}; Akhverdian VZ et al.; Five phages (PH2, PH51, PH59, PH93 and PH132) which have some characteristics common with D3112, the transposable phage of Pseudomonas aeruginosa, were isolated from clinical P . aeruginosa isolates . The phages were distributed into 4 different immunity groups . The basic criteria used for selection of transposable phages have been: 1) Morphology of a phage particle, host range, similar inactivation with antiserum; 2) Similar sizes of phage genomes; 3) The presence of a variable non-phage nucleotide sequences covalently linked to phage genome DNA, which could be identified using restriction endonucleases or by heteroduplex analyses . The DNAs of the new phages are resistant to treatment with BamH1 endonuclease, like the DNAs of phages D3112, B39 and B3 described earlier . The restriction maps of the phage genomes are constructed. J Med Microbiol, 1984 Oct, 18(2), 261 - 70 Penicillin-binding proteins, porins and outer-membrane permeability of carbenicillin-resistant and -susceptible strains of Pseudomonas aeruginosa; Livermore DM; Reduced cell permeability and target penicillin-binding protein modification were investigated as mechanisms of intrinsic resistance in strains of Pseudomonas aeruginosa resistant to carbenicillin (MIC greater than 128 mg/L) independently of beta-lactamase production . The carbenicillin-resistant strains were also remarkably resistant to other beta-lactams, quinolones, tetracyline and chloramphenicol, whereas carbenicillin-hypersusceptible strains (MIC less than 2 mg/L) were very sensitive to these antimicrobial compounds . These observations suggested a non-specific mechanism of resistance involving reduced permeability of the outer layers of the bacterial cell . However, carbenicillin-resistant and carbenicillin-sensitive strains had identical porin levels and the target penicillin-binding proteins of carbenicillin-resistant (MIC 256-2048 mg/L), carbenicillin-sensitive (MIC 64 mg/L) and carbenicillin-hypersusceptible (MIC 0.015 mg/L) strains were equally sensitive to beta-lactams . Thus, subtle changes in porin function or additional outer-membrane barriers regulating permeability may be involved in intrinsic resistance. Biochim Biophys Acta, 1984 Sep 7, 801(1), 32 - 9 Purification of NADP-dependent glutamate dehydrogenase from Pseudomonas aeruginosa and immunochemical characterization of its in vivo inactivation; Smits RA et al.; The 'high ammonia pathway' enzyme glutamate dehydrogenase (NADP+) is inactivated in cells of Pseudomonas aeruginosa when the stationary phase of growth is reached . Purified glutamate dehydrogenase (NADP+) appeared to be a protein composed of six identical subunits with a molecular weight of 54 000 . With antibodies raised against purified enzyme it was found that glutamate dehydrogenase (NADP+) inactivation is accompanied by a parallel decrease in immunologically reactive material . This suggests that glutamate dehydrogenase (NADP+) inactivation is caused or followed by rapid proteolysis. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S759 - 68 Predictors of response to therapy for infections caused by Pseudomonas aeruginosa; Platt R; Data from 410 courses of cefsulodin therapy for infections caused by Pseudomonas aeruginosa were used to determine the factors that correlated with three outcomes: bacteriologic cure, clinical response, and the occurrence of adverse effects . The factors that were evaluated were site of infection, number of infected sites, prior antibiotic therapy, concurrent antibiotic therapy, maximum daily dose of cefsulodin, pretreatment status (blood pressure, white blood cell count, hemoglobin and creatinine levels, liver function tests), age, sex, and assignment to cefsulodin via randomization . Stepwise logistic regression analysis was used to determine the factors that contributed independently to the outcome . Regression analysis indicated that three factors were significantly associated with bacteriologic cure: age, site of infection, and pretreatment hemoglobin values . Regression analysis indicated that the following four variables were significant correlates of satisfactory clinical response: site of infection, the presence of more than one infected site, diastolic blood pressure before therapy, and prior antibiotic therapy . Regression analysis also indicated that two factors, maximum daily dose of cefsulodin and duration of therapy, were the only significant predictors of the occurrence of adverse effects. Antimicrob Agents Chemother, 1984 Sep, 26(3), 295 - 9 Piperacillin plus vancomycin in the therapy of febrile episodes in cancer patients; Jadeja L et al.; Piperacillin and vancomycin were used as initial empirical therapy for 211 febrile episodes in cancer patients . The response rate in 95 episodes of documented infection was 72% . The response of bacteremias, soft tissue infections, and pneumonias was 78, 71, and 38%, respectively . The response in infections caused by gram-negative organisms was 73% . Only 6 of 10 Pseudomonas aeruginosa infections responded to therapy, although the organisms were sensitive in vitro to piperacillin . Of 14 infections caused by gram-positive organisms, 12 responded to this combination . No major side effects were observed with this regimen . Although the overall response rate with this antibiotic combination was comparable with other regimens used for neutropenic patients, superior results might be obtained by combining piperacillin with an extended-spectrum cephalosporin or an aminoglycoside. Trop Geogr Med, 1984 Sep, 36(3), 301 - 2 Pseudomonas septicaemia following tribal tatoo marks; Mathur DR et al.; It is tradition in Northern Nigeria to make tribal tatoo marks on the face of a newborn, commonly on both sides of the angle of the mouth . A case of fatal septicaemia due to Pseudomonas aeruginosa following such tribal tatoo marks is reported. Am Rev Respir Dis, 1984 Sep, 130(3), 502 - 4 Pathogenesis and prevention of nosocomial pneumonia in a nonhuman primate model of acute respiratory failure; Crouch TW et al.; Nosocomial pneumonias, usually due to gram-negative bacilli, occurred in 13 consecutive baboons that underwent endotracheal intubation, prolonged deep sedation, and paralysis during studies of acute respiratory failure . Serial bacteriologic studies demonstrated colonization of the oropharynx by pathogenic bacteria within 24 to 48 h of instrumentation, followed by aspiration of colonizing organisms into the tracheobronchial tree . Specimens obtained from the lung periphery remained sterile for at least 24 h longer than the proximal airways . Despite the presence of multiple pathogenic species in oropharyngeal and tracheobronchial secretions, pneumonias were usually due to a single species selected from those colonizing more proximal regions . In an attempt to prevent pneumonias, we added 3 measures to the management of the next 19 animals: meticulous aspiration of oropharyngeal secretions, topical instillation of polymyxin B, and prophylactic administration of ampicillin beginning 3 days prior to study . These measures reduced the prevalence of colonization with Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus, and only 3 of the 19 animals developed pneumonia . This dramatic reduction of pneumonias is explained in part by prevention of colonization by highly invasive organisms . These data indicate that manipulation of the bacterial flora of the upper respiratory tract may provide an effective approach to the prevention of nosocomial pneumonias. Am J Med, 1984 Sep, 77(3), 442 - 50 Moxalactam plus piperacillin versus moxalactam plus amikacin in febrile granulocytopenic patients; Winston DJ et al.; In a prospective randomized trial, febrile granulocytopenic patients received either moxalactam plus piperacillin or moxalactam plus amikacin as initial empiric antimicrobial therapy . Most patients were also given prophylactic vitamin K . The overall response rates for the two regimens were similar (105 of 136, or 77 percent, for moxalactam plus piperacillin versus 107 of 136, or 79 percent, for moxalactam plus amikacin) . For Pseudomonas aeruginosa infections, the response rate was better in patients receiving moxalactam plus amikacin (seven of nine versus one of five, p = 0.06); two patients treated with moxalactam plus piperacillin experienced relapse of P . aeruginosa bacteremia in association with the emergence of beta-lactam-resistant P . aeruginosa isolates . On the other hand, bacteremic enterococcal superinfections occurred in seven patients receiving moxalactam plus amikacin but in none given moxalactam plus piperacillin (p = 0.02) . Serious side-effects were minimal with both regimens, and nephrotoxicity was less common in patients receiving moxalactam plus piperacillin (two of 136 versus six of 136, p = 0.28) . There was no antibiotic-related hemorrhage . These results suggest that the overall efficacy and toxicity of moxalactam plus piperacillin and moxalactam plus amikacin are similar . Moxalactam/piperacillin therapy may be limited in certain patients by the emergence of beta-lactam-resistant P . aeruginosa, whereas enterococcal superinfections may complicate moxalactam/amikacin therapy. J Clin Pathol, 1984 Sep, 37(9), 1014 - 7 Sequential study of C reactive protein in neonatal septicaemia using a latex agglutination test; Hindocha P et al.; The usefulness of serial study of C reactive protein in the early detection of neonatal septicaemia was evaluated in a neonatal unit using a commercially available latex agglutination slide test as a rapid screening method and electroimmunoassay as a reference method for C reactive protein determination . A positive latex test was obtained in 11 infants with verified septicaemia (positive blood culture), two infants with clinically evident infection but without bacteriological confirmation, one infant with recurrent chest infection due to Pseudomonas aeruginosa, and one infant who showed signs of birth asphyxia with meconium aspiration, but was not infected . Positive latex test results correlated with raised concentrations of C reactive protein, measured by immunoassay . In some instances, however, concentrations of C reactive protein in excess of 12 mg/100 ml gave weaker agglutination results in the slide test, which could be interpreted as negative results . In a sequential study of the infected infants, 6.3% of the values recorded on a slide test were false negatives . In contrast, false positive values were observed on a slide test in 1.9% of 27 non-infected infants . The higher percentage of false negative values may be due to the presence of excess antigen in the sera of some infected children . It is suggested that the latex test should be carried out on suitable dilutions of serum . Although the slide test may reliably indicate infection at an early stage in neonates, the C reactive protein response is non-specific, as seen in a non-infected infant who showed signs of birth asphyxia with meconium aspiration . Provided the non-specific nature of the C reactive protein response is recognised, the latex test may be a useful serum measurement for early diagnosis of neonatal septicaemia of the newborn . The test has the advantage of being performed easily, quickly, and cheaply. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S769 - 74 The outlook for prevention and treatment of infections due to Pseudomonas aeruginosa; Young LS et al.; Control measures based on careful hospital surveillance are aimed primarily at minimizing environmental sources of Pseudomonas aeruginosa . Other important aspects of epidemiologic control include aggressive evaluation of outbreaks and limitation of antimicrobial use . Potent new antimicrobial chemotherapy has been developed, with most new agents of the beta-lactam and aminoglycoside classes . In spite of these developments, the likelihood of drug resistance seems great and the search for novel compounds continues . Of greatest appeal are approaches that augment host defences . Replacement or supplementation of circulating phagocytic cells is conceptually attractive, but this approach has encountered major technical problems and complications . More recently, there has been important progress in developing immunologic approaches aimed at augmenting circulating antibodies . Development of monoclonal antibodies and new methods for preparing hyperimmune globulins has produced forms of intervention that must be tested by clinical trials, but not all patients may benefit from augmentation of circulating antibodies to P . aeruginosa. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S744 - 50 Cefsulodin therapy for infections due to Pseudomonas aeruginosa in patients with burns; Heimbach DM; This multicenter trial compared treatment with either cefsulodin or reference antibiotics (gentamicin, tobramycin, amikacin, or ticarcillin) in 67 patients with Pseudomonas aeruginosa infection and burn injury . Safety of treatment was evaluated for all 67 patients; clinical efficacy, for 29; and bacteriologic efficacy, for 26 . The average daily dose and duration of treatment for the 37 cefsulodin-treated patients were 5.6 g and 10.3 days, respectively . The percentage of total body surface burned was greater than or equal to 50% for 40% and greater than or equal to 25% for 85% of the patients . Rates of bacteriologic cure for 30 sites of infection were 64% (7/11) for skin and skin-structure infections treated with cefsulodin or reference antibiotics; 100% (1/1) for respiratory tract infections treated with cefsulodin and 33% (2/6) for those treated with reference antibiotics; and 100% (1/1) for septicemia treated with a reference antibiotic . Overall bacteriologic and clinical efficacy for cefsulodin treatment was 67% (8/12) and 73% (11/15), respectively, and for treatment with a reference antibiotic was 56% (10/18) and 64% (9/14), respectively . Cefsulodin was found to be safe and comparable in efficacy to reference antibiotics in this patient population. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S728 - 33 Cefsulodin therapy for osteomyelitis due to Pseudomonas aeruginosa; Pottage JC Jr et al.; The results of treating chronic Pseudomonas aeruginosa osteomyelitis with cefsulodin at Rush-Presbyterian-St . Luke's Medical Center (RPSLMC) and eight other institutions are summarized . Eleven patients whose infections were proven by bone-biopsy culture were treated with cefsulodin at RPSLMC; one received two courses of treatment . Efficacy of therapy was evaluated for eight patients, all of whom had a polymicrobial infection . The average age of the patients was 52.3 years (range, 28-85) . All had serious underlying illnesses or associated conditions . The mean inhibitory concentration of cefsulodin for the isolates of P . aeruginosa was 3.125 micrograms/ml (range, 0.78-6.25 micrograms/ml) . Two patients received concomitant therapy with antibiotics not active against P . aeruginosa . Surgical debridement was performed in six of the eight patients . A favorable response was demonstrated in six of the eight patients . Follow-up for seven patients ranged from one week to 12 months, and in the eighth patient follow-up was 32 months . One patient relapsed twice . Seven possible complications of therapy were observed in five of the 11 patients who received cefsulodin; in three of these patients cefsulodin had to be discontinued . In studies of osteomyelitis conducted at other institutions, 10 of 14 patients for whom therapy could be evaluated had a favorable response to cefsulodin . Cefsulodin is a useful agent for the treatment of chronic osteomyelitis associated with P . aeruginosa. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S711 - 20 Experience with cefsulodin therapy for lower respiratory tract infections caused by Pseudomonas aeruginosa in adults without cystic fibrosis or granulocytopenia; Nichols L et al.; Cefsulodin was administered as the sole antipseudomonal therapy to 14 adults without cystic fibrosis or granulocytopenia for infection of the lower respiratory tract caused by susceptible strains of Pseudomonas aeruginosa . At dosages of 1.0-1.5 g intravenously every 6 hr, peak serum antipseudomonal activity consistently exceeded 1:16 . Twelve patients (86%) showed a favorable therapeutic response: six (43%) with eradication of P . aeruginosa from the respiratory tract and six (43%) with persistent colonization . Two patients (14%) did not respond to cefsulodin therapy . In five cases (36%), P . aeruginosa resistant to cefsulodin appeared during the course of therapy, in two cases contributing to therapeutic failure; three strains also acquired cross-resistance to two or more other antipseudomonal beta-lactam antibiotics . Cefsulodin was well tolerated, with no evidence of organ toxicity or other adverse effects discerned . These therapeutic results are comparable with or superior to those reported with other antipseudomonal drugs studied in single-drug regimens for treatment of P . aeruginosa lower respiratory tract infections in this patient population. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S705 - 10 Treatment of lower respiratory tract infections due to Pseudomonas aeruginosa in patients with cystic fibrosis; Caplan DB et al.; Twenty-nine patients with cystic fibrosis received either cefsulodin or a reference agent (tobramycin or ticarcillin) in a randomized manner for treatment of pulmonary infections associated with Pseudomonas aeruginosa . Patients ranged in age from 12 to 30 years . Their infections were classified as mild (six), moderate (16), or severe (seven) . Fourteen patients received cefsulodin, 14 patients were treated with tobramycin, and one patient received ticarcillin . Significant clinical improvement was noted in the majority of patients in both groups . Adverse effects and development of laboratory abnormalities were uncommon in both groups . P . aeruginosa was not permanently eradicated from the sputum of any of the patients . Resistance as measured by disk susceptibility testing may have developed during and immediately after therapy in the cefsulodin group but not in those treated with reference agents . However, this did not appear to affect the clinical outcome . Results of the nonrandomized portion of this multicenter study, in which 46 patients were treated with cefsulodin, were similar to those for the randomized group . Thus, cefsulodin was shown to be as clinically effective as the reference agents in the treatment of lower respiratory tract infections due to Pseudomonas aeruginosa in patients with cystic fibrosis. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S698 - 704 Treatment of invasive external otitis with cefsulodin; Mendelson MH et al.; Thirteen patients with invasive infections of the external ear were treated with cefsulodin sodium . Eleven were elderly diabetic patients with malignant external otitis, and two were nondiabetic adults with cellulitis or chondritis of the external ear . Four of 11 patients with malignant external otitis had extensive disease, with progression of infection to the petrous apex, medial base of the skull, or parapharyngeal soft tissue . Eleven patients had granulation tissue in the external auditory canal, and three presented with cranial nerve palsies (V, VII, IX, X) . Pseudomonas aeruginosa was isolated from all patients . Minimal inhibitory concentrations of cefsulodin for the strains isolated were 1.56-6.25 micrograms/ml (mean, 3.37 microliter/ml) and minimal bactericidal concentrations were 1.56-25 micrograms/ml (mean, 5.59 micrograms/ml) . Duration of therapy was from one to 12 weeks . Nine patients had a positive clinical response, three had recurrent disease after initial improvement, and one was lost to follow-up . A positive response was correlated with a longer duration of therapy and less extensive disease; complications were minor . Cefsulodin appears to be an effective agent for the treatment of selected patients with invasive external otitis. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S678 - 88 Effect of highly potent antipseudomonal beta-lactam agents alone and in combination with aminoglycosides against Pseudomonas aeruginosa; Lerner SA et al.; The activities of ticarcillin, cefsulodin, ceftazidime, aztreonam, and imipenem, formerly known as N-formimidoyl thienamycin, were evaluated alone and in combination with aminoglycosides against 56 clinical isolates of Pseudomonas aeruginosa, which were characterized by aminoglycoside susceptibility and content of aminoglycoside-modifying enzymatic activities . All beta-lactam agents were highly active against aminoglycoside-susceptible isolates, and with few exceptions the aminoglycoside-resistant isolates were susceptible to all of the beta-lactam agents except ticarcillin . Combinations of the beta-lactam agents with aminoglycosides frequently acted synergistically, but the effect of different beta-lactam agents in combination with an aminoglycoside against individual strains was unpredictable . The presence or absence of an aminoglycoside-modifying enzymatic activity had no observed effect on synergism with tobramycin . Killing-curve experiments with strains in the presence of concentrations of a beta-lactam and an aminoglycoside that were not bactericidal alone (one-fourth the minimal bactericidal concentration) showed synergistic bactericidal action against four strains that were tested . The results demonstrate the great activity of these newer antipseudomonal beta-lactam agents and their potential for synergism with aminoglycosides. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S667 - 77 Activity of cefsulodin and other agents against Pseudomonas aeruginosa; Neu HC et al.; Cefsulodin is a novel cephalosporin that contains a pyridinomethyl substituent at position 3 of the dihydrothiazine ring and a sulfo group on the acyl side chain . Cefsulodin has a high affinity for penicillin-binding proteins of Pseudomonas aeruginosa but binds poorly to those of other bacteria . Cefsulodin has the ability to readily pass through the outer wall of P . aeruginosa and is poorly hydrolyzed by most chromosomal beta-lactamases . It is partially destroyed by the carbenicillinases of P . aeruginosa that are plasmid mediated . Cefsulodin inhibits 50% of P . aeruginosa isolates at concentrations of 2-4 micrograms/ml . Cefsulodin acts synergistically with all aminoglycosides against 20%-80% of P . aeruginosa isolates. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S657 - 66 Host defense mechanisms against pneumonia due to Pseudomonas aeruginosa; Pennington JE et al.; Pneumonia due to Pseudomonas aeruginosa is associated with unusually high mortalities . Accordingly, efforts to define better the most important components of lung defenses against this infection are justified as a prelude to defining improved management strategies . In this report, a guinea pig model of experimental aspiration pseudomonas pneumonia was employed for studies of cellular and humoral mechanisms of pulmonary defense . Animals treated with cortisone acetate plus cyclophosphamide experienced decreased survival from pneumonia, and survival rates correlated directly with the degree of myelosuppression . Numbers of pulmonary macrophages and polymorphonuclear neutrophils were reduced in drug-treated animals before impairment of macrophage antibacterial function . Thus, a reduction in numbers of phagocytes alone was sufficient to markedly reduce lung defenses . In additional experiments, normal guinea pigs were vaccinated with a lipopolysaccharide pseudomonas vaccine . Improved survival from pneumonia correlated with high titers of type-specific, heat-stable opsonic antibody . It is concluded that adequate numbers of lung phagocytes, plus type-specific opsonic antibody, represent the ideal status for lung defense against P . aeruginosa infection. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S643 - 56 Biochemical and physiologic basis for susceptibility and resistance of Pseudomonas aeruginosa to antimicrobial agents; Sabath LD; The mechanisms involved in the susceptibility and resistance of Pseudomonas aeruginosa to antimicrobial agents are varied . For the beta-lactam agents, susceptibility of the organism is dependent on penetration of the outer membrane, binding to target proteins, absence of significant beta-lactamases, and, possibly, the initiation of cell wall lysis . Susceptibility to aminoglycosides is based on membrane permeation and transport and specific binding to the 30S ribosomal subunit . Antipseudomonal activity of the polymyxins is related to their binding to membrane phospholipids, with subsequent disruption of the membrane; and activity of tetracycline and erythromycin, which is pH-dependent, affects protein synthesis . Resistance to beta-lactam agents is mediated through beta-lactamases, the Id and V enzymes being especially important in P . aeruginosa . Other postulated mechanisms of resistance include the presence of a permeability barrier, insensitivity of target sites, decreased binding, and "trapping." Decreased binding to the S12 protein (often termed the P10 protein in references to streptomycin), decreased active transport, and enzyme-mediated modification are the major mechanisms responsible for resistance to aminoglycosides . The factors involved in resistance to tetracycline and erythromycin remain unclear . The emergence of resistance during a single course of beta-lactam therapy is a special problem with P . aeruginosa and may be due to acquisition of resistance genes, cross-infection, selection or induction of resistance in some variants, or mutation. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S627 - 42 Epidemiology of infections due to Pseudomonas aeruginosa; Morrison AJ Jr et al.; Pseudomonas aeruginosa is responsible for an increasing proportion of infections acquired in the modern hospital setting . It accounts for 8.5% of all nosocomial infections and has an attack rate of 36 infections per 10,000 hospital discharges . P . aeruginosa represents the single most frequently isolated pathogen in patients with nosocomial pneumonia and burn-wound infections . The organism's bioepidemiology is linked to its ability to thrive in marginal econiches, and its ascendency as a nosocomial pathogen parallels the evolution of high-technology intensive care units, the large numbers of immunocompromised patients, and the liberal use of antibiotics . The reservoirs and modes of transmission for this organism are reviewed along with recent studies aimed at the prevention of both colonization and infection by this organism. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S617 - 26 The virulence of Pseudomonas aeruginosa; Pollack M; Pseudomonas aeruginosa is an opportunistic pathogen whose adaptability, ubiquitousness, and pathogenicity are closely related . Both cell-associated and extracellular products of P . aeruginosa contribute to its virulence . Surface structures, including pili and the polysaccharide capsule or glycocalyx, appear to mediate the initial attachment of P . aeruginosa to its prospective host, thus permitting colonization . Extracellular enzymes such as alkaline protease, elastase, phospholipase C, and exotoxin A degrade infected tissues and promote bacterial invasion . When dissemination occurs, systemic disease results, often with fatal consequences . Although extracellular enzymes of P . aeruginosa figure prominently in local disease processes, exotoxin A and endotoxin are primarily responsible for systemic disease . The most protective antibodies presently known are directed toward the nontoxic portions of P . aeruginosa lipopolysaccharides that serve no known virulence function per se . However, there is preliminary evidence that the protective activity of these opsonic antibodies may be augmented by toxin-neutralizing antibodies directed toward the lipid A moiety of endotoxin and exotoxin A. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S603 - 7 The clinical challenge of infections due to Pseudomonas aeruginosa; Young LS; A hundred years have elapsed since the first isolation of Pseudomonas aeruginosa . Most of the early infectious processes were uncommon, but experimental studies of pathogenesis anticipated recent work . Today we recognize P . aeruginosa as a pathogen of major importance in immunocompromised patients, patients with cystic fibrosis, and patients with breached anatomic defenses . Multiple virulence factors have been identified that may account for, possibly in concert, the ability of this organism to cause disease even in normal hosts . Immunologic approaches to control or treatment offer some promise, as does the development of new antibiotics . The outlook for treatment and control of infections due to P . aeruginosa seems dependent on better understanding of pathogenesis, improved understanding of host defenses, and the most advantageous use of new antimicrobial agents. Aust Vet J, 1984 Sep, 61(9), 277 - 9 Characterisation of isolates of Pseudomonas aeruginosa from sheep; Burrell DH et al.; Fleece rot isolates of Pseudomonas aeruginosa were characterised in terms of biochemical reactions, serological typing and production of keratinase, lipase and the potentially dermal necrotic enzymes exotoxin A, protease, elastase phospholipase and lecithinase . The similarities generally obtained between these characteristics of isolates from sheep and man suggests a role for P . aeruginosa and mechanisms of pathogenesis in the development of the dermatitis associated with fleece rot. Methods Find Exp Clin Pharmacol, 1984 Sep, 6(9), 487 - 9 In vitro susceptibilities of mucoid Pseudomonas aeruginosa isolates from cystic fibrosis patients against azthreonam, netilmicin and piperacillin; Flournoy DJ et al.; Minimum bacteriostatic (MIC) and bactericidal (MBC) levels were done on 37 clinical isolates of mucoid Pseudomonas aeruginosa from cystic fibrosis patients against azthreonam, netilmicin and piperacillin . Results show that piperacillin had the greatest bacteriostatic activity; however there was more likely to be a significant disparity between MIC and MBC with this drug . Netilmicin was less active than piperacillin, but there was less difference between MICs and MBCs . Azthreonam was the least active compound tested. Jpn J Antibiot, 1984 Sep, 37(9), 1652 - 60 {Clinical laboratory approach for estimating effective administrative dose of cefsulodin}; Uete T et al.; Reliability of cefsulodin (CFS) disc sensitivity test for estimating approximate values of MICs and its utilization for evaluation of proper administrative dose were studied against 106 strains of Pseudomonas aeruginosa and Staphylococcus aureus isolated from clinical materials using 2 different kind of discs . The disc results were compared with MICs determined using agar dilution method at inoculum level of 10(6) CFU/ml . The results of CFS disc susceptibility test with 8 mm diameter disc (Showa) and 6 mm diameter disc (Wako), both of them contained 30 micrograms, were well correlated with MICs . It is capable to use disc results for estimation of approximate value of MICs . For interpretation of CFS disc tests, three category system has been used in USA and Europe, but four category system in Japan . MIC break points proposed for classifying bacteria into three categories of susceptibility: resistant (R) MIC greater than 32 micrograms/ml, moderately susceptible (MS) MIC 16 approximately 32 micrograms/ml, and susceptible (S) MIC less than or equal to 8 micrograms/ml . Those in four category system were as follows: MIC less than or equal to 3 micrograms/ml, 3 micrograms/ml less than MIC less than or equal to 15 micrograms/ml, (+) 15 micrograms/ml MIC less than or equal to 60 micrograms/ml, (-) MIC greater than 60 micrograms/ml . Based on CFS pharmacokinetic data and the recommended dosage schedule (less than 2 g a day), MIC break points less than 3 micrograms/ml and less than 15 micrograms/ml, appear to be more useful than that of less than or equal to 8 micrograms/ml and less than 32 micrograms/ml for evaluating a proper administrative dose level.(ABSTRACT TRUNCATED AT 250 WORDS) Can J Microbiol, 1984 Sep, 30(9), 1118 - 24 Experimental studies of the pathogenesis of infections owing to Pseudomonas aeruginosa: elastase, an IgG protease; Holder IA et al.; Pseudomonas aeruginosa elastase, but not alkaline protease, degraded pooled, normal, human IgG in vitro and this degraded IgG lost its protective effect when used to treat burned, P . aeruginosa infected mice . Plasma IgG levels in burned, uninfected mice declined immediately postburning, but remained relatively constant thereafter; the levels in burned, P . aeruginosa infected mice continued to decline until death ensued . Infection of burned mice with an elastase+ strain caused the IgG decline, while infection with an elastase- strain did not, suggesting that elastase production caused the in vivo decline in plasma IgG . Local treatment with the protease inhibitor alpha 2-macroglobulin, of burned mice infected with an elastase+ organism, reduced the IgG decline observed in control mice . These data support the hypothesis that P . aeruginosa elastase acts as an IgG protease both in vitro and in vivo and gives insight into how this enzyme may act as a virulence factor in P . aeruginosa. Antimicrob Agents Chemother, 1984 Sep, 26(3), 417 - 8 Comparative in vitro activities of enoxacin (CI-919, AT-2266) and eleven antipseudomonal agents against aminoglycoside-susceptible and -resistant Pseudomonas aeruginosa strains; Bassey CM et al.; The in vitro activity of enoxacin (CI 919, AT 2266), a new oral quinolone carboxylic acid compound, was compared with those of gentamicin, tobramycin, amikacin, azlocillin, piperacillin, aztreonam, moxalactam, imipenem, cefsulodin, ceftazidime, and cefoperazone against 101 aminoglycoside-susceptible and 105 aminoglycoside-resistant Pseudomonas aeruginosa strains . Among these 206 P . aeruginosa isolates were 25 strains with known mechanisms of resistance to amikacin . The activity of enoxacin was similar to that of tobramycin against aminoglycoside-susceptible strains, with MICs of 1.0 to 2.0 micrograms/ml and 0.5 to 1.0 microgram/ml, respectively, for 90% of the strains . Enoxacin was the most active agent in this in vitro study against aminoglycoside-resistant P . aeruginosa strains, with MICs of 2.0 to 4.0 micrograms/ml for 90% of the strains . Strains with enzymatic resistance to amikacin were more resistant to beta-lactams (except enoxacin and imipenem) than were strains with decreased permeability. Antimicrob Agents Chemother, 1984 Sep, 26(3), 408 - 9 Activity of apalcillin against Pseudomonas aeruginosa; Hollick GE et al.; The in vitro activity of apalcillin was tested against 107 clinical isolates of Pseudomonas aeruginosa, and the results were compared to those for piperacillin, mezlocillin, azlocillin, and carbenicillin . MIC analysis showed that 97% of the isolates were susceptible to piperacillin, 97% were susceptible to apalcillin, 93% were susceptible to azlocillin, 87% were susceptible to mezlocillin, and 84% were susceptible to carbenicillin. Antimicrob Agents Chemother, 1984 Sep, 26(3), 339 - 42 Bactericidal activity of ceftazidime in serum compared with that of ticarcillin combined with amikacin; Standiford HC et al.; We compared the bactericidal activity of serum attained 1 and 6 h after the termination of infusions of either ceftazidime (2 g) or ticarcillin plus amikacin (5 g and 7.5 mg/kg, respectively) in 6 volunteers against a panel of the most common pathogens found in the blood of febrile granulocytopenic cancer patients . Ceftazidime consistently produced significantly higher serum bactericidal titers at both 1 and 6 h against all species of gram-negative bacilli . Its performance against Pseudomonas aeruginosa was especially impressive . The geometric mean titer against this organism was 1:41 at 1 h, contrasted with 1:12 for ticarcillin plus amikacin (P = 0.025) . However, for Staphylococcus aureus, the geometric mean serum bactericidal titer of ceftazidime was 1:3.6 at 1 h and undetectable at 6 h . Ceftazidime shows promise as single-agent therapy for serious gram-negative bacillary infections . Whether this promise is fulfilled and whether the observed antistaphylococcal activity is adequate for empiric therapy in infected granulocytopenic patients need further investigation. Ann Microbiol (Paris), 1984 Sep-Oct, 135B(2), 121 - 36 Structural alterations in the envelope of a gentamicin-resistant rough mutant of Pseudomonas aeruginosa; Galbraith L et al.; Comparative studies of a gentamicin-sensitive strain (P28-0) of Pseudomonas aeruginosa and a gentamicin-resistant mutant (P23-800) have been carried out . No aminoglycoside-modifying enzymes were detected in extracts of the mutant . Electron microscopy of thin sections and the loss of O-antigenicity suggested that resistance of the mutant to gentamicin was related to an alteration in the outer membrane . Analysis of the lipopolysaccharide (LPS) components of the cell walls revealed significant differences . The LPS from strain P28-0 was typical of wild-type P . aeruginosa strains of Habs serotype O6, with quinovosamine and aminogalacturonic acid as O-specific aminocomponents . The LPS from the resistant mutant lacked the O-specific polymer, but had a core oligosaccharide similar to that of the parent strain . Both LPS were rich in phosphorus, part of which was present in triphosphate residues . Although the 31P nuclear magnetic resonance spectra of the LPS differed in some respects, these differences did not seem to correlate with the disparity in sensitivity to gentamicin of the two organisms. J Antimicrob Chemother, 1984 Sep, 14(3), 221 - 9 Pseudomonas aeruginosa beta-lactamase as a defence against azlocillin, mezlocillin and piperacillin; Jacobs JY et al.; Azlocillin, mezlocillin and piperacillin are weak substrates for the chromosomal beta-lactamase of Pseudomonas aeruginosa, and hydrolysis kinetics were calculated . Enzyme function in the living cell was studied by comparing antibiotic activity against a typical Ps . aeruginosa strain with inducible beta-lactamase expression with antibiotic activity against beta-lactamase uninducible and constitutive mutants . The inducible organism was less sensitive than its uninducible mutant to all three agents; this difference was more apparent at high inocula than low and in broth than in agar . These differences involved both enzyme induction and selection of genotypically enzyme derepressed variants . The penicillins were not, however, efficient beta-lactamase inducers at low concentrations and their activity against the inducible organism was antagonized by more potent inducers . Secondary inducers did not antagonize antibiotic activity against beta-lactamase uninducible and constitutive organisms . The beta-lactamase constitutive mutants were highly resistant to the three antibiotics tested. J Bacteriol, 1984 Sep, 159(3), 958 - 64 Isolation and characterization of an alginase from mucoid strains of Pseudomonas aeruginosa; Linker A et al.; Strains of Pseudomonas aeruginosa which produce an alginate-like slime polysaccharide were shown to also synthesize an intracellular enzyme which can degrade these polysaccharides and the seaweed alginic acids . The enzyme acts as an eliminase introducing delta 4,5 unsaturation into the uronic acid moiety . It appears to be a polymannuronide lyase which degrades the polysaccharides, depending on their uronic acid composition, to a series of oligosaccharides, the smallest of which is a disaccharide . L-Guluronic acid linkages are not split . The Pseudomonas alginase resembles other bacterial alginases and enzymes from molluscs but differs in some important properties, such as extent of degradation and linkage preference . Nonmucoid forms of the organism produce detectable but much lower amounts of enzyme. Am Rev Respir Dis, 1984 Sep, 130(3), 444 - 9 Pulmonary bacterial clearance and alveolar macrophage function in septic shock lung; Shennib H et al.; The association between the pulmonary bacterial clearance and the development of septic shock lung has been demonstrated in porcine and canine experimental models . In order to elucidate the role of the pulmonary reticuloendothelial system in bacterial clearance, the functions of alveolar macrophages (AM) obtained by bronchopulmonary lavage were studied . Five piglets were infused intravenously with Pseudomonas aeruginosa labeled with tritiated thymidine at 3 to 6 X 10(8) CFU/kg/min . Septic shock and manifestations like those of the adult respiratory distress syndrome developed within 1 h, and the pigs died within 2 to 3 h . Pulmonary bacterial clearance was 93% initially, and progressively decreased to 29%, as Pao2 decreased and lung water increased . The number of bacteria in the serial lung biopsy specimens increased steadily, although the distribution was not homogeneous . Differential centrifugations, repeated washings, and scintillation countings of the lavage fluid showed that in vivo AM phagocytosis was nil, despite the abundant bacteria found in the lavage fluid . However, when these AM were washed and tested in vitro in the presence of optimal concentrations of opsonin and oxygen, their phagocytic capability was well preserved, and was not significantly different from that of prebacterial infusion baseline values . It is concluded that in the septic shock lung, the lung clears bacteria not primarily by AM uptake but by other mechanisms, such as mechanical leakage into the pulmonary space, or by pulmonary intravascular leukocyte uptake . The apparent AM dysfunction in vivo is not intrinsic, and is likely to be caused by microenvironmental factors, such as lack of adequate opsonin and oxygen. Infect Immun, 1984 Sep, 45(3), 756 - 60 Effect of Pseudomonas aeruginosa cytotoxin on thymidine incorporation by murine splenocytes; Obrig TG et al.; The interaction of highly purified Pseudomonas aeruginosa cytotoxin (PAC) with murine splenocytes was examined . Added at culture initiation, PAC (0.1 to 0.5 microgram/ml) inhibited subsequent {3H}deoxythymidine incorporation measured between 42 to 48 h . Incorporation of {3H}deoxythymidine was inhibited 50% in lipopolysaccharide-, phytohemagglutinin-, and concanavalin A-stimulated cultures by 0.20, 0.32, and 0.39 microgram of PAC per ml, respectively . It is concluded that PAC exhibits a narrow inhibitory concentration response range of 0.1 to 0.5 microgram/ml which, secondarily, is affected by the presence of mitogens . Antitoxin added at splenocyte culture initiation, directly after PAC, yielded greater than or equal to 86% protection against PAC inhibition of {3H}deoxythymidine incorporation . Addition of antitoxin to cultures at different times after PAC demonstrated a time-dependent loss of antitoxin protective effect over a 12-h period, indicating that PAC became cell associated and refractory to antitoxin within this time period . PAC preincubated with splenocytes at 4 degrees C for less than or equal to 1 h could not be removed by washing of cells and was fully inhibitory to {3H}deoxythymidine incorporation when these cells were cultured at 37 degrees C . This finding was confirmed by demonstrating that 125I-labeled PAC bound immediately to cells . It is concluded that PAC action on splenocytes is dose- and time-dependent and consists of a two-phase process: (i) a very rapid binding of PAC to the cell surface available to antitoxin, and (ii) a slower toxicity development phase of ca . 12 h, during which PAC becomes refractory to antitoxin. Infect Immun, 1984 Sep, 45(3), 748 - 55 Serum sensitivity of a Pseudomonas aeruginosa mucoid strain; Schiller NL et al.; The susceptibility of Pseudomonas aeruginosa 144M (a mucoid strain isolated from the sputum of a cystic fibrosis patient) to the bactericidal activity of pooled fresh normal human serum (FHS) was examined . FHS at concentrations of greater than or equal to 2.5% was capable of killing greater than 95% of strain 144M . Strain 144M was killed by FHS in a dose-dependent manner . Although either immunoglobulin M (IgM) or IgG was bactericidal in the presence of complement, IgM was about 10 times as effective as IgG . However, optimal killing activity required both IgM and IgG and complement, activated by the classical pathway . A role for lysozyme in the killing of 144M was demonstrated only when low concentrations of FHS were used . In contrast to 144M, P . aeruginosa strains 144NM and 144M(SR) were totally resistant to FHS at all of the concentrations tested (up to 50%) . Neither the FHS susceptibility of 144M nor the FHS resistance of 144NM or 144M(SR) was altered by choice of growth medium, growth phase, or temperature of growth . Results of absorption studies with whole organisms, isolated outer membrane preparations, or lipopolysaccharide (LPS) from each strain suggest that the antigen(s) which binds the bactericidal immunoglobulins is accessible on the surface of 144M but not on the surface of 144NM or 144M(SR), is insensitive to trypsin treatment, and is believed to be LPS . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the three LPS preparations demonstrated that 144M LPS contained primarily lipid-A-core polysaccharide components, whereas the LPS from 144NM and 144M(SR) were heterogeneous, with various degrees of O-side-chain substitution . These results suggest that at least one target for bactericidal antibody on the surface of 144M is contained in the rough LPS of this strain. Infect Immun, 1984 Sep, 45(3), 741 - 7 Pulmonary cellular response to chronic irritation and chronic Pseudomonas aeruginosa pneumonia in cats; Thomassen MJ et al.; A model of chronic pulmonary infection was used for studying cellular events in a sequential manner . In this model, agarose beads containing Pseudomonas aeruginosa were instilled endotracheally into cats . Nine cats were inoculated with agarose beads containing P . aeruginosa, and four others were inoculated with sterile beads . With a fiberoptic bronchoscope, bronchial washings were obtained biweekly for up to 30 weeks . The quantitative pulmonary inflammatory cell response and alveolar macrophage morphology of the animals exposed to P . aeruginosa were compared with those for the animals exposed to a chronic irritant (agarose beads) . Bronchial washings of all animals before inoculation showed that 70 to 90% of the cells were macrophages . After inoculation with P . aeruginosa, a persistent inflammatory response was observed (60 to 70% granulocytes) . In the sterile-bead-inoculated group, the response was less prominent (30 to 40% granulocytes) . As early as 2 weeks after inoculation, alveolar macrophages from infected animals were larger and had cytoplasmic features that differed from those of controls . Electron microscope examination showed prominent surface alterations in alveolar macrophages from the infected cats . These alterations persisted from 2 to 12 weeks after infection . In animals inoculated with sterile beads, alveolar macrophages exhibited less extensive surface changes that had resolved by week 8 . Histologically, chronic bronchiolitis and pneumonia were more severe in the infected animals than in controls . This model of chronic inflammation and macrophage stimulation, which is similar to the chronic pneumonia of cystic fibrosis, may be a useful approach to answer questions on the role of macrophage activation in chronic lung disease. Rev Infect Dis, 1984 Sep-Oct, 6 Suppl 3, S721 - 7 Treatment of skin and soft-tissue infections with cefsulodin; Mogabgab WJ; Skin and soft-tissue infections due to Pseudomonas aeruginosa were treated with intravenous infusions or intramuscular injections of cefsulodin sodium in an open, multicenter study . A total of 40 patients were evaluated to determine the safety and clinical and bacteriologic efficacy of cefsulodin . Cefsulodin was administered alone (31 patients) or in combination with a nonantipseudomonal antibiotic (nine patients) when additional infecting organisms were present . The duration of cefsulodin therapy ranged from two to 46 days (2-12 g/day) . Twenty-five patients were treated at New Orleans hospitals for postoperative wound, traumatic wound, and skin ulcer infections with cefsulodin alone or in combination with nonantipseudomonal antibiotic . Therapy with cefsulodin (2-8 g/day) ranged from four to 37 days . P . aeruginosa was eradicated in all the patients, and all clinical responses were considered satisfactory . Fifteen patients were treated at the collaborative centers for postsurgical wound, traumatic wound, skin ulcer, cellulitis, and subcutaneous abscess infections . Therapy with cefsulodin (4-12 g/day) ranged from five to 45 days . The bacteriologic cure rate for assessable patients was 87% (13 of 15 patients), and a satisfactory clinical response was observed in 93% (14 of 15). J Hosp Infect, 1984 Sep, 5(3), 329 - 33 Preservative activity in diluted corticosteroid creams; Hugo WB et al.; The preservative efficacy of both 'Betnovate' and 'Synalar' creams diluted 1:1 with 'Unguentum Merck' was investigated . Each formulation was challenged with Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa at an initial inoculum level of approximately 1 X 10(6) viable organisms per gram of cream . All formulations tested were found to be effectively preserved against the organisms used and no viable bacteria were detected 7 days after inoculation. J Antimicrob Chemother, 1984 Sep, 14 Suppl B, 277 - 84 Treatment of severe staphylococcal infections with cefotaxime and fosfomycin in combination; Portier H et al.; In a prospective study, 23 severe staphylococcal infections (9 meningitis, 10 bone and joint infections, 3 septicaemia, 1 superinfection of a congenital varicella) were treated with cefotaxime and fosfomycin in combination . There was a synergistic effect of the combination for 14 of the 17 strains tested . Three hours after the end of the infusion, mean CSF concentrations of cefotaxime and fosfomycin were respectively at day 2 3.2 mg/l and 31.4 mg/l, at day 4 2.9 mg/l and 33.9 mg/l . All the patients with meningitis or acute bone and joint infections recovered satisfactorily without relapses . Two superinfections were observed (one systemic candidosis and one septicaemia due to Pseudomonas aeruginosa) . Clinical tolerance was good and treatment was discontinued for side effects in only three patients. Biochim Biophys Acta, 1984 Aug 28, 789(1), 37 - 43 Enzymatic inactivation of human plasma C1-inhibitor and alpha 1-antichymotrypsin by Pseudomonas aeruginosa proteinase and elastase; Catanese J et al.; Two major human plasma proteinase inhibitors, C1-inhibitor and alpha 1-antichymotrypsin, were enzymatically inactivated by Pseudomonas aeruginosa elastase and proteinase . Incubation of C1-inhibitor with the Pseudomonas enzymes at inhibitor/enzyme molar ratios of 1000:1 (elastase) or 22:1 (proteinase) resulted in cleavage of the 104 kDa intact inhibitor to an 89 kDa intermediate which retained full inhibitory activity against plasmin and plasma kallikrein . The intermediate was then cleaved to an 83 kDa inactive product . The initial non-inactivating cleavage of C1-inhibitor occurred in a region of the molecule readily accessible to limited proteolysis by both enzymes . The inactivating cleavage, however, occurred more readily with the elastase . alpha 1-Antichymotrypsin was inactivated by P . aeruginosa proteinase and elastase by limited proteolysis at inhibitor/enzyme molar ratios of 14 000:1 . The 64 kDa intact inhibitor was cleaved to form an inactive 60 kDa product, and a low molecular mass peptide fragment was observed . No stable enzyme-inhibitor complexes were detected, and no random proteolysis of the inactivated inhibitors was noted, even after prolonged incubation . Catalytic inactivation of C1-inhibitor and alpha 1-antichymotrypsin by P . aeruginosa proteinase and elastase may contribute to the tissue damage and hemorrhagic lesions which occur during pseudomonal infections. Chemioterapia, 1984 Aug, 3(4), 258 - 61 Comparative in vitro activity of aztreonam, other beta-lactam antibiotics and aminoglycosides against Pseudomonas aeruginosa; Venditti M et al.; Aztreonam, ceftriaxone, moxalactam, cefotaxime, cefsulodin, cefoperazone, piperacillin, azlocillin, carbenicillin, amikacin, gentamicin, tobramycin, sisomicin and dibekacin were tested by broth dilution against 161 isolates of Pseudomonas aeruginosa . Seventy-one of these strains were selected for their resistance to carbenicillin and aminoglycosides and classified as "multiply resistant" strains . Over all, aztreonam showed the greatest antipseudomonal activity by far, followed by ceftriaxone, moxalactam, cefotaxime and amikacin . Piperacillin, azlocillin, cefsulodin, and cefoperazone were highly active against carbenicillin and/or aminoglycoside-susceptible P . aeruginosa strains, but were also poorly inhibitory against multiply resistant isolates. Eur J Clin Microbiol, 1984 Aug, 3(4), 288 - 93 Influence of subinhibitory concentrations of antibiotics on opsonization and phagocytosis of Pseudomonas aeruginosa by human polymorphonuclear leukocytes; Milatovic D; To determine whether pretreating Pseudomonas aeruginosa with antibiotics had an effect on phagocytosis, a serum-resistant clinical isolate was incubated with one-third of the minimum inhibitory concentrations of azlocillin, carbenicillin, cefoperazone, fosfomycin, netilmicin and piperacillin respectively prior to exposure to human polymorphonuclear leukocytes . The phagocytic process was measured by assaying radiolabeled bacteria . The uptake rates of untreated and antibiotic treated bacteria did not differ when normal human serum was used for opsonization . However, when the serum was heated to inactivate the complement system, its opsonic activity for untreated as well as for fosfomycin and netilmicin treated pseudomonas was removed and phagocytosis did not take place . In contrast, bacteria pretreated with the betalactam antibiotics still underwent phagocytosis, as also confirmed by electron microscopy . Even in the presence of rabbit immune serum untreated bacteria still required the participation of the complement system for optimal opsonization, whereas bacteria treated with beta-lactam antibiotics did not. Curr Eye Res, 1984 Aug, 3(8), 1075 - 8 Inhibition by phosphoramidon of Pseudomonas aeruginosa elastase injected intracorneally in rabbit eyes; Kessler E et al.; Phosphoramidon (N-(alpha-L-rhamnopyranosyloxyhydroxyphosphinyl)-L-leucyl-L-trypto phan) is a powerful inhibitor of Pseudomonas aeruginosa elastase . The addition of this compound to an elastase solution injected intrastromally in rabbit eyes protected the corneas from the damage of the enzyme for a period of 12 hours . Phosphoramidon is comparable in this respect to the inhibitor 2-mercaptoacetyl-L-phenylalanyl-L-leucine, but is considerably more effective than its analog phosphoryl-L-leucyl-L-phenylalanine (P-Leu-Phe) . It is suggested that the rhamnopyranosyl moiety, present in phosphoramidon but not in P-Leu-Phe, is responsible for the difference in the intracorneal activity of the two phosphoramidates . Phosphoramidon as well as the mercaptoacetyl derivative might prove beneficial in the treatment of Pseudomonas aeruginosa corneal infections. Appl Environ Microbiol, 1984 Aug, 48(2), 301 - 5 Pseudomonas aeruginosa biosurfactant production in continuous culture with glucose as carbon source; Guerra-Santos L et al.; Rsan-ver, a strain of Pseudomonas aeruginosa isolated at this department, was used for the development of a continuous process for biosurfactant production . The active compounds were identified as rhamnolipids . A final medium for production was designed in continuous culture by means of medium shifts, since the formation of surface-active compounds was decisively influenced by the composition and concentration of the medium components . In the presence of yeast extract, biosurfactant production was poor . For the nitrogen-source nitrate, which was superior to ammonium, an optimum carbon-to-nitrogen ratio of ca . 18 existed . The iron concentration needed to be minimized to 27.5 micrograms of FeSO4 X 7H2O per g of glucose . A carbon-to-phosphate ratio below 16 yielded the maximum production of rhamnolipids . The final productivity dilution rate diagram indicated that biosurfactant production was correlated to low growth rates (dilution rate below 0.15 h-1) . With a medium containing 18.2 g of glucose liter-1, a biosurfactant concentration (expressed as rhamnolipids) of up to 1.5 g liter-1 was obtained in the cell-free culture liquid. Antimicrob Agents Chemother, 1984 Aug, 26(2), 275 - 6 In vitro comparison of amifloxacin and six other antibiotics against aminoglycoside-resistant Pseudomonas aeruginosa; Thompson KD et al.; The in vitro activity of the synthetic fluoroquinolone amifloxacin was compared with those of six other antibiotics: ampicillin, aztreonam, cefotaxime, cephalexin, cinoxacin, and gentamicin . Amifloxacin had the lowest 50% MIC of any of the antibiotics tested against aminoglycoside-resistant Pseudomonas aeruginosa, 4 micrograms/ml. Antimicrob Agents Chemother, 1984 Aug, 26(2), 272 - 4 Imipenem antagonism of the in vitro activity of piperacillin against Pseudomonas aeruginosa; Bertram MA et al.; The MICs of imipenem and piperacillin, alone and in combination, against Pseudomonas aeruginosa were determined in a checkerboard titration microdilution assay . A dramatic, one-way antagonism of imipenem for piperacillin was demonstrated in 28 of the 35 strains examined; antagonism was associated with the induction of a beta-lactamase. Antimicrob Agents Chemother, 1984 Aug, 26(2), 256 - 9 In vitro activities of ureidopenicillins alone and in combination with amikacin and three cephalosporin antibiotics; Moody JA et al.; The MIC and MBC activity of mezlocillin alone and in combination with two concentrations of ceftizoxime, moxalactam, and amikacin and a single concentration of cefoxitin was studied in a broth microdilution partial checkerboard against 472 strains of aerobic gram-negative and gram-positive bacteria . Azlocillin was tested alone and in the same combinations against Pseudomonas aeruginosa . Of the gram-negative bacilli tested, 38% were gentamicin resistant . Antagonism (less than or equal to a fourfold ureidopenicillin MIC increase) was observed frequently with combinations of ureidopenicillins plus cefoxitin and sporadically with ureidopenicillins plus ceftizoxime or moxalactam . Partial synergism (less than or equal to a fourfold ureidopenicillin MIC decrease) was evident with both combinations of ureidopenicillins plus amikacin and ureidopenicillins plus ceftizoxime or moxalactam, the percentage being dependent upon the individual species and combinations. Antimicrob Agents Chemother, 1984 Aug, 26(2), 181 - 6 Correlation between lipopolysaccharide structure and permeability resistance in beta-lactam-resistant Pseudomonas aeruginosa; Godfrey AJ et al.; Four beta-lactam-resistant permeability mutants of Pseudomonas aeruginosa PAO503 were studied . The resistance phenotypes were correlated to changes within the lipopolysaccharide . Two of the mutants, PCC1 and PCC19, were shown to differentiate between beta-lactams on the basis of relative hydrophobicity . The more hydrophilic antibiotics were less effective at inhibiting these strains . This phenotype was correlated to the presence of mannose, in measurable quantities, in lipopolysaccharide isolated from these strains . The other two strains, PCC23 and PCC100, differentiated between cephem antibiotics on the basis of electrical charge . The presence of a positive charge markedly increased the relative efficiency of an antibiotic . This correlation did not hold for penam derivatives, with the lower-molecular-weight, dianionic molecules being the most effective . Mutants of this type were changed in the amount of "side chain" sugars or, to minor extent, in their outer membrane protein profiles. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1984 Aug, 257(3), 409 - 13 Benzethonium chloride resistance in Pseudomonas aeruginosa isolated from clinical lesions; Nakahara H et al.; The benzethonium chloride resistance of 341 strains of Pseudomonas aeruginosa isolated from Jikei University Hospital was determined . The distribution pattern of the susceptibility to benzethonium chloride clearly revealed two peaks, and the resistance was differentiated by 1000 micrograms/ml (0.1%) of benzethonium chloride . The frequency of resistance to benzethonium chloride was 51.6% . Furthermore, the frequencies of resistance to SM, TC, CP, KM, GM, PIP, Hg, Cd, As and chlorhexidine were 42.5, 15.8, 41.3, 29.6, 14.0, 8.2, 88.3, 97.9, 97.1, and 74.5%, respectively. J Infect Dis, 1984 Aug, 150(2), 223 - 8 Mediation of the killing of rough, mucoid isolates of Pseudomonas aeruginosa from patients with cystic fibrosis by the alternative pathway of complement; Pier GB et al.; The mechanism of killing of 12 serum-sensitive strains of mucoid Pseudomonas aeruginosa isolated from patients with cystic fibrosis was investigated . A quantitative assay indicated that more than 90% of cells were killed in 50% normal human serum (NHS) . All strains failed to grow in NHS concentrations of greater than 10% . Killing was unaffected by adsorption of NHS with the mucoid bacteria or chelation with MgCl2-ethyleneglycol bis(beta-aminoethyl ether)N,N1-tetraacetate (MgCl2-EGTA) but was abolished in serum heated to 50 C for 20 min . Incubation of NHS with mucoid P . aeruginosa reduced the hemolytic capability of MgCl2-EGTA-chelated NHS against rabbit red blood cells by 56%-99% . Killing of the serum-sensitive mucoid strains was also seen in hypogammaglobulinemic serum . These data suggest that killing of such strains by NHS can occur via antibody-independent activation of the alternative pathway of complement . The importance of this finding lies in the implication that complement levels in the lungs of patients with cystic fibrosis who are colonized by these organisms are inadequate to deal with this chronic, progressive infection. J Med Microbiol, 1984 Aug, 18(1), 125 - 33 Relationship of iron and extracellular virulence factors to Pseudomonas aeruginosa lung infections; Sokol PA et al.; The iron concentration in the culture medium used to prepare the inocula influenced the virulence of Pseudomonas aeruginosa in a chronic pulmonary infection model in rats . Groups of rats were given transtracheal inocula of agar beads in which were embedded c.10(4) cfu of P . aeruginosa strain PAO and the mutants of strain PAO, Fe5 and Fe18 . When strain PAO was grown in low-iron medium before infection, it caused severe parenchymal changes including a dense mononuclear cell infiltration in the alveolar spaces, as well as intra- and peribronchial inflammation . When strain PAO was grown in high-iron medium, the pathological changes in lungs were restricted to intra- and peribronchial inflammation . Strain Fe5, in which the effect of iron on yields of elastase is deregulated, produced similar pathological changes regardless of whether it was grown in low- or high-iron media . All rats infected with strain Fe18, in which the effect of iron on yields of toxin A is deregulated, died within 48 h after infection . These data indicate that the iron concentration of the culture medium can influence the pathogenesis of P . aeruginosa in a chronic respiratory infection . These studies also suggest that the regulation of extracellular virulence factors by iron is important in the determination of P . aeruginosa virulence. Infect Immun, 1984 Aug, 45(2), 475 - 82 Kinetic analysis of microbe opsonification based on stimulated polymorphonuclear leukocyte oxygenation activity; Allen RC et al.; With Pseudomonas aeruginosa as the target microbes and polymorphonuclear leukocytes (PMNL) as effector phagocytes, the microbe-specific, immunoglobulin G (IgG)-dependent opsonic capacities of preimmune and immune sera were measured as the rate of stimulated PMNL dioxygenation of luminol yielding chemiluminescence (CL) . When the reactants other than opsonin are present in concentrations that are not rate limiting, the information-effector relationship linking specific opsonin concentration to effector PMNL stimulation is described by the rate equation: L' = k'{IgG}i, where L' is the peak CL velocity (photons per minute), k' is the proportionality constant, {IgG} is the concentration of specific opsonin, and the exponent i is the order of the reaction with respect to opsonin . Since the specific opsonins were polyclonal IgG of unknown absolute serum concentration, the reciprocal rate expression, L' = k'D-i, was employed for data presentation; D is the serum dilution (final volume/initial serum volume), and the sign of i is changed to negative . The relationships of integral, first-derivative, and second-derivative expressions of the CL response to opsonin concentration are illustrated with experimentally obtained data . Based on peak CL velocity or peak CL acceleration measurements taken over different time intervals of testing, the estimated order with respect to opsonin is highest, and probably most accurate, using the shortest test interval allowing reasonably good precision of measurement . As an alternative temporal approach, microbe opsonification kinetics are analyzed based on nodal time (Tn) measurements . The Tn is the time point separating the acceleration and deceleration phases of the PMNL oxygenation response to stimulation and as such satisfies the criterion of a selected condition of PMNL activation. Infect Immun, 1984 Aug, 45(2), 309 - 13 Immunochemical characterization of high-molecular-weight polysaccharide from Fisher immunotype 3 Pseudomonas aeruginosa; Pier GB et al.; A high-molecular-weight polysaccharide (PS) was isolated from the culture supernatant of a Fisher immunotype 3 (IT-3) strain of Pseudomonas aeruginosa . Consistent with previously reported findings for IT-1 and IT-2 PS, the preparation of IT-3 PS was found to be an immunogenic, nontoxic form of the O polysaccharide side chain on the lipopolysaccharide (LPS) . The IT-3 PS was mainly carbohydrate in composition . It was serologically and chemically identical to LPS O side chain, but distinct from that structure in molecular size and immunogenicity . The IT-3 PS was nontoxic in mice and guinea pigs, nonpyrogenic in rabbits, and greater than 1,000-fold less reactive than IT-3 LPS in gelation of the Limulus amoebocyte lysate . Preliminary analyses by gas-liquid chromatography and 13C nuclear magnetic resonance have established the structural identity of IT-3 high-molecular-weight PS and the IT-3 O side chain . IT-3 PS was immunogenic in rabbits and mice . After active immunization, mice were protected against P . aeruginosa IT-3 intraperitoneal infection and burn wound sepsis . IT-3 PS also elicited protection against challenge with an IT-5 strain of P . aeruginosa, indicating that low-level contamination of the IT-3 PS with IT-3 LPS was not responsible for the immunogenic activity . These findings demonstrate the feasibility of preparing nontoxic immunogenic IT-3 PS capable of eliciting serotype-specific protective antibodies, employing methods similar to those previously described for the isolation of PS from other P . aeruginosa immunotypes. J Immunol, 1984 Aug, 133(2), 962 - 8 In vitro T cell-mediated killing of Pseudomonas aeruginosa . I . Evi