Interference of Pseudomonas aeruginosa with immunospecific host defenses.

Pseudomonas aeruginosa, an important nosocomial pathogen, has numerous virulence factors that may interfere with unspecific host defense mechanisms (complement components, neutrophils, macrophages). Furthermore, Pseudomonas aeruginosa or substances derived from it can inhibit lymphocyte proliferative responses and alter immune responses, especially cell-mediated immune responses as evidenced by prolonged survival of skin homografts and suppression of DTH skin reaction in humans and laboratory animals. Acquired cellular resistance to Listeria monocytogenes is also suppressed by P. aeruginosa. Likely more than one mechanism is responsible for these depressed immune responses. Nevertheless, P. aeruginosa is able to interfere with macrophages and T-lymphocyte activities. The relevance of the immunosuppression with respect to host defenses against infections is discussed in the context of evidence in favor of cell-mediated immunity of P. aeruginosa.

[Bacteriologic analysis of 150 episodes of septicemia in a hematology department according to the length of hospitalization]. / Analyse bactériologique de 150 épisodes septicémiques en hématologie selon le temps d'hospitalisation.

One hundred and fifty episodes of septicaemia in patients in a haematology service were analysed as a function of the date of onset in relation to the date of hospitalisation. One hundred and three patients of the 122 patients were granulocytopenic and 97 patients (65%) had less than 500 polymorphonuclear neutrophils per microliter. The septicaemic episodes were classified according to three time periods: septicaemia starting before admission and during the first 24 hours in hospital, septicaemia occurring between day 1 and day 8 and septicaemia beginning on day 9 or later. For each period different factors have been studied, the number of septicaemic episodes, the frequency of multiple infection, the severity of the granulocytopenia, the antibiotics used compared to their sensitivity in vitro, the outcome of the septicaemia, the organisms isolated by blood culture and their sensitivity to different antibiotics. The patients with septicaemia arriving at the hospital with a fever, and those starting during the first week of hospitalisation are finally comparable, even though the level of mortality was distinctly different (33 and 17% respectively). The septicaemia starting after day 8 are more frequent and more severe (40% mortality). These late onset septicaemias are characterised by a higher frequency of Gram negative hospital infections, a high frequency of mixed infection with bacteria resistant to several beta-lactams and aminoglycosides. The observation of these differences between these septicaemias occurring in the first week and those starting after the eighth day should be taken into account in the choice of an empirical antibiotic regimen. An association of 2 or 3 antibiotics for these two situations respectively, involving beta-lactams and aminoglycosides, is proposed by the authors.

[Oxacillin and gentamicin-resistant Staphylococcus aureus: surveillance and development over a period of 6 months]. / Staphylococcus aureus oxacilline et gentamicine-résistants: survenue et évolution sur une période de 6 mois.

An outbreak of nosocomial infections caused by oxacillin and gentamicin-resistant Staphylococcus aureus occurred over a 3 month period in the intensive care unit of a 371-bed hospital. Four patients were infected. S. aureus isolates were resistant to multiple antibiotics beside oxacillin and gentamicin. They exhibited identical antibiotic susceptibility pattern and identical phage type (47/54/75/77/84/85). A subsequent survey of oxacillin-resistant S. aureus was conducted in the hospital during a 6 month period. Bacteriophage typing was performed on 52 isolates of oxacillin-resistant S. aureus. Seventeen were non typeable . Fourteen had the same phage type (or a minor variant +/- 2 numbers) as that of the previously isolated S. aureus. The antibiotic susceptibility pattern of 10 of the 14 isolates was identical to that of the epidemic strain. The antibiotic susceptibility patterns of 2 isolates differed from it with respect to the resistance to one antibiotic among those tested (these two isolates were obtained from patients that received the particular antibiotic before the isolation of the Staphylococcus). The 7 patients from whom these 12 S. aureus were isolated were staying in the intensive care unit except one who was hospitalized in this unit several months ago. Among the personnel screened, two intensive care unit nurses were found to be nasal carriers of oxacillin resistant S. aureus. One strain had the same phage type as that of the epidemic strain but its antibiotic susceptibility pattern was different. Room-mate to room-mate spread within the intensive care unit may be responsible for the perpetuation of the epidemic strain.(ABSTRACT TRUNCATED AT 250 WORDS)

[Listeriosis in obstetrical environment. Report on 10-year experience in a maternity hospital in Paris]. / La listériose en milieu obstétrical. Bilan de 10 ans dans une maternité parisienne.

Thirty six cases of listeriosis were seen in the hospital between 1975 and 1984. Ten aborted before the 28th week of pregnancy while 26 passed the 28th week of pregnancy. The incidence was about 1 per 1,000 deliveries. The bacteriological diagnosis depends on isolating the germ either from blood cultures or from multiple swabs from the child at birth, or from liquor amnii or from the placenta. The clinical events that occur in pregnancy were analysed in order to trace out the evolution of maternal listeriosis better and to work out from it a good preventive therapeutic approach. Twenty one out of the 26 women found in the month preceding delivery lassitude, often accompanied by a febrile illness which suggested a primary infection with the listeria. The blood cultures from four of them showed L. monocytogenes and treating these ladies with antibiotics enabled the pregnancy to go to term. Thirteen of the infants that were affected developed favourably but 8 died. Four of these died in utero and two (twins) died after being born healthy. The seriousness of the illness in the fetus seems to have a direct relationship to the time between the primary infection and the delivery. Blood cultures make it possible to diagnose the condition at the first sign of infection whatever the clinical features of the case are.

[Rupture of the membranes and amniotic infection. Apropos of 3000 cases]. / Rupture des membranes et infection amniotique. A propos de 3000 cas.

This work shows the effect of a policy of reducing the amounts of antibiotics prescribed, and reports on the effect on the rate of infection in a maternity unit where systematic antibiotic cover for patients with premature rupture of the membranes was stopped. Breaking of the waters with loss of liquor makes infection of the contents of the sac almost inevitable; but we have found over a period of five years that with the exception of certain strains of Group B streptococci infection with bacteria from vaginal flora rarely gives rise to severe infection in the infant. This balance sheet was drawn up: 350 infections of the liquor in 13.540 deliveries, which is 2.5%. Infection of the liquor by definition implies that the infant will be contaminated; but in fact the baby was infected in only 0.6% of births--which figure is no higher than in other series. Bacteria found in the vaginal flora: streptococci and anaerobes are responsible for 92% of amniotic infections, streptococcus B being first in frequency responsible for 41.36% of amniotic infections and 47.5% of neonatal infections. The low percentage, 5.4% of Gram negative Bacilli can be attributed to their absence when antibiotic cover is given. Neonatal infections usually improve quickly with a narrow-spectrum antibiotic and the one we gave most often was penicillin G. Careful watch on women with premature rupture of the membranes, accompanied by repeated bacteriological control makes it possible to avoid systematic antibiotic therapy and to allow the antibiotic sensitive bacteria to return to their primary role, if by chance infection of the amniotic contents, which is usually benign, occurs.

[Risk of neonatal Streptococcus B infection]. / Risque infectieux néo-natal à streptocoque B.

23 cases of contamination with streptococcus group B have been seen after premature rupture of the membranes. Mothers and fetuses have been affected. The systematic study of swabs or liquor or cervical discharge carried out on the mother since the time her membranes had ruptured show that in 74 per cent of cases studied contamination existed within the first 24 hours. Giving antibiotics to the mother before delivery gave very variable results. These multiple tests, before and around the time of birth, made it possible to detect the children at risk of infection and to start antibiotic therapy with a narrow spectrum antibiotic of the type Penicillin G. The clinical progress of these children, which is usually favourable, gives no reason for postponing prophylactic cover antibiotic treatment when the membranes have ruptured prematurely.

Enhanced killing of Pseudomonas aeruginosa by human polymorphonuclear leukocytes in presence of subinhibitory concentrations of carbenicillin and ticarcillin.

The effect of carbenicillin and ticarcillin on the killing of Pseudomonas aeruginosa was studied with an in vitro system using peripheral blood polymorphonuclear (PMN) leukocytes collected from human donors. No corticosteroid was given to the donor prior to leukocytes collection by a continuous flow cell separator. The assay was carried out with or without serum. P. aeruginosa yield after a 4 hour-incubation was estimated by colony counting. In Hanks' balanced salt solution, P. aeruginosa strains 74 and 78 were resistant to human PMN leukocytes. The presence of subinhibitory concentrations of carbenicillin or ticarcillin (1/10th the minimal inhibitory concentration (MIC) for P. aeruginosa 74, 1/4th the MIC for P. aeruginosa 78) enhanced the bactericidal activity of human leukocytes. Difference between the numbers of bacteria recovered with PMN cells and without cells increased with concentration of carbenicillin or ticarcillin. The synergistic effect was not observed when serum (heated fetal calf serum or heated pooled human serum) was used. The mode of action of carbenicillin and ticarcillin on bactericidal activity of phagocytic cells was not elucidated, but we suggest the effect is due not to action on the phagocytic cells themselves but on the microorganisms.

[Leptospiroses in New Caledonia. Reports of 32 cases diagnosed between 1973 and 1980]. / Leptospiroses en Nouvelle-Calédonie. Bilan des case diagnostiqués de 1973 à 1980.

This first study about human leptospiroses in New Caledonia reports 32 cases diagnosed between 1973 and 1980. They are typical forms with hepatonephritis in 90 % of cases. Serogroup Icterohaemorrhagiae is predominating (75 %), followed by Canicola and Australis. The disease is spread throughout the whole territory with two foci in the suburbs of the main town where there are irrigated market gardens. Contamination is indirect by contact with water infected by rodents.

[Development of HIV 1 antigenemia during treatment with azidothymidine (AZT): follow-up of 90 patients for a year]. / Evolution de l'antigénémie VIH 1 lors du traitement par l'azidothymidine (AZT): suivi de 90 malades à un an.

VIH 1 antigenaemia has a significant value in the follow-up of patients treated with AZT. This study of 90 patients (55 ARC - 35 AIDS), each receiving AZT for more than a year, 200 mg every 4 hours, demonstrates the prognosis value of antigenaemia at Day 0, as well as its therapeutic indication value. However, at term and under this treatment, the significance of this virological data has to be reconsidered. Various kinetic patterns are described according to the clinical status and the CD4+ cells count.

Effect of active and passive immunization on the development of experimental Pseudomonas aeruginosa pyelonephritis in mice.

Experimental pyelonephritis was produced in mice by the intravenous injection of Pseudomonas aeruginosa. Immune response to infection was studied by passive hemagglutination antibody titers. Vaccination of mice with live P. aeruginosa or culture filtrates (Pseudomonas antigen) induced antibodies and resulted in a high degree of protection against death and pyelonephritis following subsequent hematogenous challenge with the homologous strain. Transfer of immune serum protected mice against death following infection with the homologous strain and with a heterologous strain. However, immune serum failed to protect mice from kidney infection by the heterologous strain. These data indicate that immune serum seemed to protect against early, overwhelming bacteremia but did not prevent a chronic course of kidney infection by a heterologous strain.

[Comparison of in vitro bacteriostatic effect of five betalactamins against Pseudomonas aeruginosa (author's transl)]. / Comparaison de l'effet bactériostatique in vitro de cinq bétalactamines actives sur Pseudomonas aeruginosa.

In vitro activity of two penicillins (ticarcillin and azlocillin) and three cephalosporins (cefoperazone, cefsulodin and ceftazidime) was compared against one hundred clinical isolates of Pseudomonas aeruginosa originated in two different Paris hospitals. Twenty strains were resistant to carbenicillin at a concentration of 128 mg/l. Minimal inhibitory concentrations (MICs) were determined by a twofold agar dilution method. The required ceftazidime concentration to inhibit 90 p. cent of the carbenicillin-susceptible isolates was 1,9 mg/l. To achieve the same inhibition, 3,9 mg of cefsulodin, 12 mg of cefoperazone, 14 mg of azlocillin or 38 mg of ticarcillin per liter were needed. Against the 209 carbenicillin-resistant isolates, ceftazidime remained active at concentrations lower than 2 mg/l in 90 p. cent of the cases. To obtain such an inhibition with the other antibiotics higher concentrations were needed.

[Computer technology in the interpretation of aminoglycoside determinations]. / Apports de l'informatique dans l'interprétation des dosages d'aminosides.

Given the difficulty of interpreting the results of aminoglycoside determinations using current methods, we decided to use data processing in order to help practitioners in their prescriptions of these drugs. Our software has numerous advantages. Results can be interpreted even before obtention of the steady-state and whatever the interval between specimen taking and drug administration, which permit different modalities of blood sampling. Data storage enables the operator to make retroactive studies in order to establish better correlation between blood concentrations and side effects. This method gives practitioners the necessary pharmacological data for rapid adjustments in aminoglycosides dosage.

Suppression of cellular immunity to Listeria monocytogenes by activated macrophages: mediation by prostaglandins.

We previously demonstrated the suppression of cell-mediated immunity to Listeria monocytogenes by Pseudomonas aeruginosa-induced, macrophage-like cells. The present study was undertaken to evaluate the mechanism for this suppression. P. aeruginosa supernatant was shown to activate macrophages by the criteria of increased bactericidal capacities and increased attachment to glass surfaces. Acquired cellular resistance to L. monocytogenes could also be inhibited by macrophages from L. monocytogenes-pretreated mice. The depression of acquired immunity by P. aeruginosa- or L. monocytogenes-activated macrophages did not appear to be due to a reduction of antigenic stimulus after nonspecific macrophage activation. In contrast, our findings suggest that suppression is mediated by activated macrophages through a prostaglandin-dependent mechanism. In vivo administration of aspirin blocked the immunosuppressive effect of P. aeruginosa- or L. monocytogenes-activated cells. Moreover, the suppressive activity of supernatants of macrophages from Listeria-infected mice was reversed when indomethacin was present during supernatant generation. Finally, prostaglandin E1 treatment in vivo profoundly inhibited the induction of cell-mediated immunity to L. monocytogenes. The possible role and mechanism of prostaglandin in suppressing cellular immunity to intracellular bacteria are discussed.

The bacteriology of cavitating pulmonary infections and empysema. Studies of transtracheal aspirates and pleural fluid.

A prospective study of bacteriology in 14 cases of cavitating pulmonary infections and empyema is reported. Bacteriologic results were based on transtracheal aspirates or pleural fluid. Appropriate anaerobic bacteriologic methods were employed. Anaerobic bacteria were recovered in 11 patients (79%); they were the only pathogens isolated in 6 patients. The predominant species were Fusobacterium nucleatum, Bacteroides melaninogenicus, Bacteroides fragilis and Peptostreptococcus. Aerobic bacteria were present in 7 patients. The results indicate that anaerobes play a key role in most cases of cavitating pulmonary infections and empyema, and that proper culture of adequat specimens will generally establish the bacteriological diagnosis.

[Synergistic activity between ticarcillin, azlocillin, cefsulodin, ceftazidime and tobramycin or amikacin against Pseudomonas aeruginosa (author's transl)]. / Activité synergique des associations ticarcilline, azlocilline, cefsulodine, ceftazidime et tobramycine ou amikacine vis-à-vis de Pseudomonas aeruginosa.

Activity of azlocillin, cefsulodin, ceftazidime, ticarcillin in combination with amikacin or tobramycin was investigated against 17 Pseudomonas aeruginosa isolates. Synergistic activity was evaluated by the microtiter checkerboard technique. The bactericidal effect of the antibiotic combination was determined by subculturing onto agar and into broth. Synergistic activities of cefsulodin and ticarcillin combined with amikacin or tobramycin were similar in the inhibitory as well as in the bactericidal tests. Synergistic effects of the combination of ceftazidime and amikacin or tobramycin were moderate or indifferent in the inhibitory and bactericidal tests. The combination of azlocillin and amikacin or tobramycin produced synergistic effects greater in bactericidal tests than in inhibitory tests. The bactericidal synergistic activities of the combinations of azlocillin, cefsulodin, ticarcillin were similar. There was no difference between amikacin and tobramycin combined with a beta-lactamine. Antagonism was not observed. A synergistic effect of the combinations was observed against 4 isolates resistant to tobramycin and/or ticarcillin. However the result of the interaction seemed to depend upon the level of resistance to the antibiotic : if the MIC or the MBC of either antibiotic in the test combination was very high, synergy could not be achieved.

Depression by Pseudomonas aeruginosa of two T-cell-mediated responses, anti-Listeria immunity and delayed-type hypersensitivity to sheep erythrocytes.

Pseudomonas aeruginosa was studied for its effects on T-cell-mediated responses in mice, as exemplified by anti-Listeria immunity and delayed-type hypersensitivity to sheep erythrocytes. Immunity to Listeria monocytogenes was measured by quantitation of bacteria in spleens and mortality; delayed hypersensitivity to sheep erythrocytes was tested by the footpad reaction. Three different preparations of P. aeruginosa were used: the supernatant of a heat-killed culture, living bacteria, and heat-killed organisms. Similar results were obtained with the three preparations. Administration of P. aeruginosa 24 h before Listeria infection reduced the resistance to the secondary challenge, as measured by increased bacterial multiplication in the spleen and rate of mortality. Cell transfer experiments showed that pretreatment of normal recipient mice with P. aeruginosa prevented them from being adoptively immunized against a Listeria challenge infection with spleen cells from immune donors. They also showed that treatment of donors with P. aeruginosa before immunization affected the capacity of their spleen cells to protect normal recipients against Listeria. Furthermore, spleen and peritoneal exudate cells obtained from mice given P. aeruginosa were capable of preventing immunization of normal recipients against Listeria. Similar results were obtained when the delayed hypersensitivity response to sheep erythrocytes was studied. The suppressive activity of P. aeruginosa-treated spleen cells was lost by removing adherent cells. Conversely, the adherent, heat-killed, anti-immunoglobulin-treated spleen cells exerted a suppressor effect. It thus appears that P. aeruginosa injection changes macrophage and T-lymphocyte activities and results in the development of adherent, macrophage-like suppressor cells in the spleen and peritoneal cavity.

[Comparative bactericidal activity of cefsulodin and ceftazidime on Pseudomonas aeruginosa]. / Activité bactéricide comparée de la cefsulodine et de la ceftazidime sur Pseudomonas aeruginosa.

This research concerns the bacteriostatic and the bactericidal activity of two beta-lactams (cefsulodin and ceftazidime) on ten strains of Pseudomonas aeruginosa affected by carbenicillin. Additionally to classical approaches in the broth and agar technics, a method of culture on filter membrane is used. The results obtained after a 2 hours and 24 hours contact are reported. The resulting values of minimum inhibitory concentrations are comparable. As far as minimum bactericidal concentrations values are concerned, there is no significant difference between the two methods or between the two antibiotics. The analysis of the bactericidal effect of a 2 hours contact allows no inference relative to the comparative effect of the two antibiotics. Each strain of P. aeruginosa has its specific behaviour, and there seems to be no way to extrapolate from their minimum inhibitory concentrations the bactericidal effect of cefsulodin and ceftazidime.

Effect of imipenem (N-formimidoyl-thienamycin) on the in-vitro lymphocyte proliferation.

Imipenem, a new carbapenem, was tested for its inhibitory or stimulatory effects on concanavalin A- and phytohaemagglutinin-stimulated and unstimulated proliferation (measured by 3H-thymidine uptake) of murine splenocytes and thymocytes. Addition of imipenem at concentrations of 10-50 mg/l induced lymphocyte transformation in unstimulated and mitogen-stimulated lymphocytes. Since imipenem stimulated blastogenesis at concentrations achievable in serum when used therapeutically, these results may have potential clinical significance.

Kinetics of interleukin-1 production by macrophages during infection with Listeria monocytogenes.

Production of interleukin-1 (IL-1) by peritoneal macrophages from mice inoculated intravenously with Listeria monocytogenes was measured at increasing intervals of infection. IL-1 activity in the 24 h macrophage supernatants was determined by using the thymocyte PHA co-mitogenesis assay. IL-1 production increased as the infection progressed, reached a peak on the 9th or 10th day and then declined progressively to approach normal values by the 20th day. Our data on the kinetics of IL-1 levels during an acute infection with L.monocytogenes are discussed in relationship to the development of cell-mediated immunity and its regulation by macrophages.