Antibiotics 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 OR thesaurus 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, ampicillin and gentamicin. Clindamycin, cefoxition and imipenem induce enhancement of chemotaxis, whereas cefotazime, 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).

Animals↗

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In vitro effect of cefodizime, imipenem/cilastatin and co-trimoxazole on dexamethasone and cyclosporin A depressed phagocytosis.

Phagocytosis is an important part of the host defense against infection. Antibiotics can influence phagocytic function. In the present study, leukocyte metabolic response to phagocytic challenge by latex was assessed in relation to in vitro addition of cotrimoxazole, imipenem/cilastatin, cefodizime, dexamethasone (DXM), and/or cyclosporin A (CsA). Using latex particles as phagocytic challenge, glucose-1-14C utilization and 14CO2 production were measured by liquid scintillation counting. The phagocytic response was impaired by in vitro addition of DXM or CsA and this setup was used as an experimental model of immunodepression. The addition of co-trimoxazole to control samples (without DXM or CsA) depressed the response to latex challenge, whereas imipenem and cefodizime had a neutral effect. In the presence of DXM, co-trimoxazole induced a further decrease. The depressive effect of DXM was partially neutralized in the presence of cefodizime. With CsA depression, co-trimoxazole also induced a further decrease, imipenem had a neutral effect, while cefodizime partially restored the CsA suppressed reaction. Co-trimoxazole depressed the phagocytic response, imipenem had a neutral effect, whereas cefodizime restored the experimentally induced immunosuppression.

Anti-Bacterial Agents↗

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Urea kinetic modelling: comparison of three methods.

It has been claimed that computed urea kinetic (UK) modelling in haemodialysed patients for the estimation of protein intake and of the relation between total dialyser urea clearance and distribution volume (Kt/V) leads to an overestimation of protein catabolic rate (PCR). In the present study three different methods of kinetic modelling for the determination of PCR and Kt/V are compared in 15 patients. The first method (MI) is the direct quantification method based on the collection of all urea eliminated from the body. The two other methods are based on an iterative computed calculation. The second method (MII) is the urea kinetic modelling method as described by Sargent. Dialyser clearances were measured directly and not estimated by theoretical extrapolation. The third method described here (MIII), is based on the indirect calculation of urea distribution volume (Vw) according to Watson and of dialyser clearances from this Vw and from pre- and post-dialysis urea concentrations. All three methods result in PCRs that are not significantly different (MI: 1.04 +/- 0.29; MII: 1.07 +/- 0.28; MIII: 1.05 +/- 0.24 mg/kg BW per 24 h; p greater than 0.05). When the results are correlated, the following results are obtained: MI vs MII: r = 0.76, p less than 0.001; MI vs MIII: r = 0.78, p less than 0.001; MII vs MIII: r = 0.90, p less than 0.001. For Kt/V virtually identical results were obtained for each of the methods under study. In conclusion, all methods under study seem equally reliable in determining mean PCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

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Waterborne Pseudomonas septicemia.

A small cluster of waterborne septicemias with Pseudomonas species occurred in a dialysis unit despite regular control of bacterial contents of tap water and dialysate conforming to preset standards. Pseudomonas aeruginosa, P. maltophilia, and/or P. vesicularis were found in the blood cultures of three patients in whom four pyrogenic reactions developed. The cluster occurred only in patients treated with formaldehyde-reused dialyzers. Pseudomonads were also cultured from the effluent of two dialyzers reprocessed with formaldehyde and not yet used; these two dialyzers had extremely low formaldehyde concentrations. The tap water used for dialyzer rinsing in the reuse procedure contained only 220 colony forming units/ml pseudomonads. The problem appeared to be related to the inadequate mixing of the sterilant with the tap water used in the automated reprocessing device--in the absence of an alarm for this failure. After immediate discontinuation of the reuse procedure with this device (that had been in use for 6 years) no further septicemic episodes were registered. It is concluded that septicemias may occur despite a bacteriologic contamination level of water conforming to preset standards. Such episodes can be avoided only by total water decontamination.

Aged↗

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Relationship between phagocyte metabolic function and years of maintenance dialysis.

An index of the activation of NADPH-oxidase in the production of free radicals is CO2 production by the hexose monophosphate shunt of polymorphonuclear cells (PMN). 14CO2 production from glucose-1-C14 was studied as an indicator of PMN function after addition of latex or zymosan to predialysis whole blood, and correlated with the years spent on hemodialysis. In a series of 49 patients, a nadir in PMN metabolic activity, when compared with healthy controls, was reached in a subgroup treated for less than 24 months (n = 24, latex: 109.5 +/- 10.1 vs. 233.7 +/- 11.8; zymosan: 181.9 +/- 18.9 vs. 407.8 +/- 19.3 DPM/10(3) PMNs; p less than 0.01). In patients treated by dialysis for longer than 24 months, PMN metabolic function was significantly better, resulting in partial correction of the defect for both latex and zymosan. Phagocyte CO2 production in response to latex or zymosan correlated significantly with years of dialysis treatment (r = 0.63 and 0.56, respectively, n = 49; p less than 0.001). These findings may have implications for phagocyte reactivity towards infection, bioincompatible dialyzer membranes, and renal transplantation.

Energy Metabolism↗

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In vivo solute extraction by a new polysulphone membrane with low ultrafiltration capacity.

High flux polysulphone (PS600, Fresenius) is a highly biocompatible membrane, but the high ultrafiltration (UF) capacity limits its clinical applications. In the present study a new PS (PS400) with an UF coefficient in the range of cuprophan (CU) but a biocompatibility like high flux PS was evaluated. Dialysis efficiency with PS400 was compared to dialyzers with the same surface, at similar blood flows. Overall extraction of UV-absorbing compounds was higher with PS400 (P less than 0.01). The extraction of the individual compounds, hippuric acid and parahydroxy-hippuric acid was also higher for PS400 (P less than 0.01 resp. less than 0.05). The fall in white blood cells after 15 min. of dialysis was from 6.5 +/- 1.5 to 1.7 +/- 0.6 for CU (-83%), and from 8.6 +/- 1.7 to only 7.4 +/- 1.7 x 10(3) cells/mm3 (-14%) for PS400 (P less than 0.01 versus CU). Ultrafiltration characteristics were similar for both dialyzers.

Biocompatible Materials↗

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