Severin Ringoir

Immunomodulating effects of antibiotics : Literature review

SummaryAntibiotics can interact directly with the immune system. This is a review of the immunomodulating effects of antibiotics. The Medline database on CD-ROM was searched for the years 1987 to 1994 using the following search string: “thesaurus explode antibiotics / all AND (thesaurus explode immune-system / drug effects ORthesaurus immune-tolerance / drug effects).” Aspects of the immune system studied were aspects of phagocyte functions: phagocytosis and killing, and chemotaxis and aspects of lymphocyte functions: lymphocyte proliferation, cytokine production, antibody production, delayed hypersensitivity and natural killer-cell activity. In order to quantify and to compare immunomodulatory properties of antibiotics we calculated an “immune index,” defined as: number of positive statements — number of negative statements/total number of statements. Concerning phagocytosis, positive effects were observed for cefodizime, imipenem, cefoxitin, amphotericin B and clindamycin and negative effects for erythromycin, roxithromycin, cefotaxime, tetracycline, amplicillin and gentamicin. Clindamycin, cefoxitin and imipenem induce enhancement of chemotaxis, whereas cefotaxime, rifampicin and teicoplanin decrease chemotaxis. Regarding lymphocyte proliferation, cefodizime has the strongest stimulating effect, whereas tetracycline has the strongest negative effect. Except for erythromycin and amphotericin B the number of statements reported is too small to be conclusive for the interpretation of effects on cytokine production. Erythromycin and amphotericin B appear to stimulate cytokine production. As to antibody production, cefodizime has the strongest positive effect, whereas josamycin, rifampicin and tetracycline have marked negative effects. For delayed hypersensitivity and the natural killer-cell activity the number of statements is too small for any single antibiotic to be conclusive. There are three markedly immuno-enhancing antibiotics (imipenem, cefodizime and clindamycin) and eight markedly immuno-depressing antibiotics (erythromycin, roxithromycin, cefotaxime, tetracycline, rifampicin, gentamicin, teicoplanin and ampicillin).ZusammenfassungAntibiotika können direkt mit dem Immunsystem in Wechselwirkung treten. Im Folgenden geben wir eine Übersicht über immunmodulierende Wirkungen von Antibiotika. Medline Datenbasen auf CD-ROM für die Jahre 1987–1994 mit den Stichworten “thesaurus explode antibiotics / all AND (thesaurus explode immune-system/ drug effects ORthesaurus immune-tolerance / drug effects)” wurden befragt. Die immunologischen Studien betrafen Aspekte der Phagozytenfunktionen: Phagozytose und Abtötung sowie Chemotaxis und Aspekte der Lymphozytenfunktion, Lymphozytenproliferation, Zytokinproduktion, Antikörperbildung, Überempfind-lichkeitsreaktion vom verzögerten Typ und natürliche Killerzellaktivität. Um immunmodulierende Eigenschaften von Antibiotika quantifizierbar und vergleichbar zu machen, wurde ein wie folgt definierter “Immunindex” berechnet: Zahl positive Aussagen — Zahl negativer Aussagen/Gesamtaussagen. Positive Wirkungen auf die Phagozyten wurden mit Cefodizim, Imipenem, Cefoxitin, Amphotericin B und Clindamycin gemacht. Bei Erythromycin, Roxithromycin, Cefotaxim, Tetracyklin, Ampicillin und Gentamicin wurden negative Effekte beobachtet. Clindamycin, Cefoxitin und Imipenem induzieren eine Verstärkung der Chemotaxis. Auf die Lymphozyten-proliferation hat Cefodizim den stärksten Stimulationseffekt, Tetrazyklin hat den stärksten negativen Effekt. Die Wirkung auf Zytokinproduktion kann nur für Erythromycin und Amphotericin B beurteilt werden, bei allen anderen Substanzen reichen die Daten hierfür nicht aus. Erythromycin und Amphotericin B führen offensichtlich zu einer Stimulation der Zytokinproduktion. Auf die Antikörperbildung hat Cefodizim die stärkste positive Wirkung, deutlich negative Effekte wurden mit Josamycin, Rifampicin und Tetrazyklin beobachtet. Für die verschiedenen Antibiotika liegen nicht genügend Studien zur Überempfindlichkeitsreaktion vom verzögerten Typ oder zur Natural Killer Cell Aktivität vor. Drei der Antibiotika haben ausgeprägte fördernde Wirkung auf das Immunsystem (Imipenem, Cefodizim, Clindamycin), acht haben ausgeprägt immunsuppressive Wirkung (Erythromycin, Roxithromycin, Cefotaxim, Tetrazyklin, Rifampicin, Gentamicin, Teicoplanin und Ampicillin).

Morbidity and Mortality of Central Venous Catheter Hemodialysis: A Review of 10 Years’ Experience

The morbidity and mortality of hemodialysis by internal central venous catheterization in the subclavian and internal jugular positions are reviewed. A follow-up study was performed in our unit over 10 years (786 catheterizations). The most frequent complications were inadequate flow (7.6%) inadvertent withdrawal (5.6%) and bacteremia (5.1%). The overall complication rate was 27.2%. Kinking (p less than 0.001), bleeding (p less than 0.01) and bacteremia (p less than 0.05) occurred more frequently in patients with chronic renal failure, compared to patients with acute renal failure. Inadvertent withdrawal was the only complication observed more frequently in the internal jugular than in the subclavian position (10.8 vs. 4.3%; p less than 0.01). Bacteremia occurred more frequently after prolonged periods of catheterization (greater than 10 days). No fatal complications were observed. To obtain a more accurate idea about mortality, two supplementary large groups were studied: a review of 11 published series (1,542 catheterizations) and a questionnaire-based survey of 16 dialysis centers (approximately 4,000 catheterizations). Six fatalities were registered: 1 due to septicemia (in the literature review) and 3 due to traumatic perforation of the cardiac or the vessel wall, 1 to septicemia and 1 to air embolism (in the questionnaire-based survey). Based on the three different groups studied, the mortality of catheter dialysis could be estimated to be between 0 and 1.25/1,000 catheterizations.

Diquat intoxication: Report of two cases and review of the literature

Animal experiments have suggested that diquat is less toxic than the more widely used paraquat. In this paper, nine previously reported cases of diquat intoxication are reviewed, together with the description of our personal observations in two additional patients. These two patients, like four other patients described in the literature, died from complications involving the gastrointestinal tract, brain and kidneys. Thus, diquat intoxication is apparently not as innocent as was originally thought. In this paper, special attention has been given to the major clinical differences between diquat and paraquat intoxication. In contrast with the latter, severe diquat intoxication induces gastrointestinal fluid sequestration and is associated with cerebral hemorrhagic lesions and a higher incidence of severe acute renal failure. Despite an asymptomatic clinical interval of up to 48 hours after ingestion, hemoperfusion should be started as soon as possible to prevent toxic levels of diquat in tissue.

Correction of Deficient Phagocytosis During Erythropoietin Treatment in Maintenance Hemodialysis Patients

Studies on the influence of erythropoietin (EPO) on granulocyte or monocyte function are scant. In this study, the effect of EPO on polymorphonuclear cell (PMN) respiratory burst activity was evaluated in a double-blind, placebo-controlled study in 22 patients on maintenance hemodialysis. As an index of phagocyte respiratory burst activity, the increase in 14CO2 production from labeled glucose-1-C, after challenge with latex and zymosan, was measured on predialysis whole blood samples, before and after EPO-treatment. As controls, 56 nonuremics and 49 non-EPO-treated hemodialysis patients were evaluated. Before EPO treatment 14CO2 production was depressed to 75.7% (latex) and 54.6% (zymosan) of healthy controls (P less than 0.01). A marked improvement was observed after a mean treatment period of 4 months (latex, 115 +/- 12 to 172 +/- 14; zymosan, 178 +/- 19 to 412 +/- 36 dpm/10(3) PMN, P less than 0.01). Placebo treatment induced no changes. The improvement became more pronounced with prolongation of treatment. A significant correlation between hematocrit and 14CO2 production was observed in the EPO treatment group (latex: n = 44, r = 0.47, P less than 0.05; zymosan: n = 44, r = 0.57, P less than 0.001). No correlation was found with serum ferritin. We conclude that the depressed phagocyte glycolytic activity of hemodialyzed uremics is normalized during correction of anemia by EPO. This may be attributed to factors other than a reduction in the body iron stores.

Pseudomonas septicemia due to deficient disinfectant mixing during reuse.

We describe a cluster of four septicemias with pseudomonas, that occurred in a unit performing formaldehyde reuse of capillary dialyzers. Samples of blood, heparin solutions, dialysate and effluent of reused dialyzers, were evaluated bacteriologically and upon the adequacy of the reuse procedure. Pseudomonas aeruginosa, vesicularis and/or xanthomonas maltophilia were found on the blood cultures obtained during the septicemic reactions, and in the effluent of two reprocessed dialyzers not yet used (> 104 CFU/ml). These two dialyzers had also extremely low formaldehyde concentrations (0.0014 and 0.005% versus the expected 4%). Membrane and antibiogram characteristics of a Pseudomonas aeruginosa strain, recovered from the blood cultures in one patient, and of a strain found in the effluent of one of the two contaminated reprocessed dialyzers, were the same. The problem was attributed to the inadequate mixing of the disinfectant with the tap water used in the automated reprocessing device, in the absence of an alarm disclosing this failure.

High intravenous doses of methylprednisolone for acute cadaveric renal allograft rejection.

In a group of 48 patients with a renal cadaveric allograft 38 acute rejection episodes were treated by increasing the daily prednisolone doses to 300 mg the first day, 200 mg the second day and 100 mg the third day, gradually tapering down over a matter of weeks. In a second group of 48 patients 39 acute rejections were treated by 1 g of methylprednisolone intravenously on alternate days with a maximum of four injections. Rejection treatment was successful in 26 of 38 in the first group (68%) and in 30 of 38 in the second group (76%). Complications such as gastrointestinal bleeding, aseptic necrosis and diabetes were more frequent in the first series.

Role of medullary hemodynamics in the natriuresis of drug-induced renal vasodilation in the rat.

In contrast to most renal vasodilators, such as acetylcholine (ACh), secretin increases renal blood flow in the dog without a marked effect on sodium excretion (UNaV). To investigate this observation, we studied the relationship between renal vasodilation, UNa»V, and papillary plasma flow (PPF) in rats, infused either with ACh or secretin into the aorta at the level of both renal arteries. ACh significantly increased GFR, PAH clearance, and UNaV (Δ + 0.35 ml/min, + 2.11 ml/min and + 1.77 /iEq/min, respectively; P < 0.05). PPF rose from 50 ± 2.6 ml/min 100 g (mean ± SE) in control rats to 91 ± 4.7 ml/min 100 g after ACh (P < 0.001). Despite a similar increase in PAH clearance after secretin (+ 2.21 ml/min; P< 0.01), UNaV remained unchanged and PPF was only slightly, although significantly, increased (from 50 ± 2.6 ml/min 100 g to 65 ± 2.75 ml/min 100 g; P < 0.05). Both total kidney and papillary vasodilation, and the increase in UNaV after ACh were blocked by previous administration of meclofenamate (M), a prostaglandin inhibitor. No effect of M in secretin-infused rats was observed. In conclusion, the relationship between total renal vasodilation and natriuresis was dissociated with secretin, but not with ACh. However, a relationship between the natriuresis and influence on papillary hemodynamics was observed with both vasodilators. Finally, the renal hemodynamic and natriuretic effects of ACh are probably mediated by prostaglandin release. Circ Res 47: 839-844, 1980

The Uraemic Syndrome

The uraemic syndrome is characterized by a deterioration of biochemical and physiologic functions, in parallel with the progression of renal failure, and results in important but variable symptomatology. Although well known for more than 160 years (1), our knowledge about the responsible factors remains inconsistent and incomplete. The quest for ‘the’ uraemic toxin has been overemphasized, not taking into account the uraemic syndrome as the result of a cumulative retention of innumerable compounds. The extrapolation of in vitro data to the clinical situation has sometimes resulted in incorrect hypotheses, whereas trivial factors with a potential bias on the results have not been taken into account

Salmonella Typhimurium Infections in Renal Transplant Patients

Five patients with Salmonella typhimurium infection after a renal cadaveric graft are described. Salmonella were isolated from the urine of four patients, from the stool of one patient, from the blood of two patients, from the hip joint of one patient and from the cerebrospinal fluid of one patient. Infections were difficult to eradicate and necessitated prolonged antibiotic treatment. Renal function only deteriorated after the infection in some patients; salmonellosis could have triggered the rejection of the graft. Impaired cell-mediated immunity due to immunosuppressive drugs may be considered to be a predisposing factor for this kind of infection. Higher humoral antibody titers against Salmonella were found in the patients most clinically ill.

Estimation of parameters in a two-pool urea kinetic model for hemodialysis

A two-pool, variable volume urea kinetic model for estimation of solute removal in hemodialysis is solved analytically, and closed form expressions are presented for urea concentration in both compartments, both during dialysis and between dialyses. This approach also includes an estimation of the extent of the post dialysis rebound phenomenon of urea concentration. A method is presented to estimate values for the urea generation rate G, the distribution volume V and its partition in two compartments with volumes alpha 1V and alpha 2V (alpha 1-alpha 2-1), the total clearance K, and intercompartmental transfer coefficient X. To apply this analysis, several measurements are needed as input; the urea concentration at the end of a dialysis, the evolution of this concentration during the next dialysis, with at least four measurements including the initial and the final concentration, the volume of the dialysate, and its urea concentration. The main results are: the magnitude of the rebound is approximately proportional to alpha 2(2) K/X; the accuracy of the parameter estimation does not improve much further by taking more than six measurements during dialysis.