Dirk van der Waaij

Infection prevention in granulocytopenic patients by selective decontamination of the digestive tract

In a controlled prospective randomized trial we studied the effect of selective decontamination of the digestive tract (SDD) in granulocytopenic patients on the frequency of infections. By SDD it was aimed to suppress the pathogenic Gramnegative micro-organisms and yeasts without affecting the non-pathogenic anaerobic flora. This anaerobic flora was maintained intact because of its value for the colonization resistance of the gastrointestinal tract. SDD was accomplished by oral administration of nalidixic acid or co-trimoxazole or polymyxin E to suppress growth of aerobic Gram-negative bacteria, and amphotericin-B to inhibit growth of yeasts. Gram-negative or yeast infections occurred in the control group 18 times in 12 patients; in the decontaminated group two times in two patients (P < 0.01). Clinical infections occurred 15 times in 12 control patients and four times in three SDD treated patients (0.01 < P < 0.05). While nine patients in the control group died with an acquired infection none died in the SDD treated group (P < 0.01). It is concluded that SDD is a promising and widely applicable method of infection prevention. It decreases the need for treatment in a ‘protected environment’.

Development and persistence of multi-resistance to antibiotics in bacteria; an analysis and a new approach to this urgent problem.

The intestinal microflora may have more influence on infectious diseases, than the mere control of growth of opportunistic micro-organisms by colonisation resistance (CR) and unspecific stimulation of the immune system. In compromised patients the CR may become decreased for several reasons but mostly because antibiotics reach the intestine during treatment. The consequence of a CR-decrease is that antibiotic-resistant opportunistic micro-organisms may increase in numbers in the gut. In this context, it is hypothesised that if the CR could be maintained at a normal level, the risk for maintenance and spread of resistant strains could be mitigated. Such maintenance requires absence of active antibiotic substance in the gut. This might be brought by the inactivation of antimicrobial agents by intestinal contents. Intra-intestinal inactivation has been described to occur along two possible routes: (1) inactivation by chemical binding or absorption and (2) by enzymatic destruction. Secondly, the composition of the intestinal microflora should be maintained at a normal level in case of other reasons for CR-decrease than antibiotic activity. Comprehensive study of the composition of normal microflora and the strains of species which play a role in CR with techniques which have become available during last decade, is recommended as well as the application of certain pre- and probiotics. It is concluded that antibiotic inactivation may be an ancient strategy of nature which should become incorporated in antibiotic treatment. Antibiotic use and development of resistance may have occurred when ecosystems formed several billions of years ago. Protection against antibiotics produced by newcomers into the ecosystem may have developed as it was necessary to maintain locally available nutrients for the inhabitants of the ecosystem. Should this hypothesis be correct, it is plausible that antimicrobial inactivation by antibiotic inactivating molecules is ubiquitous. In the ecosystem of the digestive tract, molecules involved in inactivation may predominantly be formed by microorganisms.

Computer processing of microscopic images of bacteria: morphometrY and fluorimetry

Several techniques that use computer analysis of microscopic images have been developed to study the complicated microbial flora in the human intestine, including measuring the shape and fluorescence intensity of bacteria. These techniques allow rapid assessment of changes in the intestinal flora and could apply equally to other complex microbial ecosystems.