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EFFECTS OF ANTIMICROBIAL THERAPY UPON
DIGESTIVE TRACT MICROFLORA
Laboratory for Medical Microbiology, University of Groningen, INTRODUCTION
(van der Waaij et al., 1971; van der Waaij, 1982) predominantly anaerobic and/or in the intestines, either following pressed, or not sensitive and largely un- and mix with it to establish in the course tentially pathogenic, are generally sensi- of several days a steady state concentra- tive and killed (van der Waaij, 1982). In which may fluctuate with serum levels.
of the antibiotic(s) that have reached the "overgrowth" (van der Waaij, 1979; Nord et al., 1984). Such high concen- trations of potentially pathogenic bacte- fer of the concentration established.
invaded (van der Waaij et al., 1972).
tive suppression of sensitive bacteria in This event is called "translocation" the oropharynx and/or the gut, either the SELECTIVE SUPPRESSION OF BOWEL FLORA
largely unaffected (van der Waaij et al., are resistant to the antibiotic used.
"selective decontamination" (Sleijfer et this condition is beneficial as it is asso- implications of antibiotic therapy for the suppressed by antibiotic therapy (van FAECAL CARRIAGE OF RESISTANT BACTERIA
cycline (Gross et al., 1982). In view of the shift in general practice prescribing testinal tract and not at the site of infec- scription of tetracyclines decreased with changes in resistance rates in relation to association of those bacteria with oppor- tract (Eickhoff, 1979) and urinary tract so that direct comparison is difficult.
increased from 19% to 48% (Burt and ence of antibiotic treatment (Watanabe, Woods, 1976). A study of an extremely studies from the sixties and early seven- ties of the faecal carriage of antibiotic resistant bacteria in normal individuals, streptomycin (Gardner et al., 1969).
teropathogenic Escherichia coli showed resistant to ampicillin and 29% to tetra- ANTIBIOTIC RESISTANCE IN ENTEROBACTERIACEAE FROM HEALTHY
VOLUNTEERS
antibiotic prescribing habits of 15 local antibiotic resistant faecal E. coli in nor- reported in 1966 (Smith and Halls, the intermediate in adults and the lowest in children of less than four years of age resistant E. coli. Approximate analysis portant factor. Linton et al. (1972) how- ever, did not mention the fact that chil- population (Leading article, 1974).
Smith and Halls found in 19 of 20 rep- riage rates of resistant strains in children resentative E. coli from healthy subjects chance of acquiring resistant strains.
ported both in the absence (Petrocheilon carriage of antibiotic resistant bacteria in of antibiotic treatment (van der Waaij et (Williams Smith, 1975; Leading article, rural non-farming families by Linton et a very long time (Hartley and Rich- mond, 1975). The explanation for the than the prevalence in children (64%).
also in a high percentage (63%) resistant of the colonization resistance associated flora in children than in adults. Whether in the Netherlands (van der Waaij et al., intestinal contents (faeces) and may vary where in this monograph, it is likely that particularly as far as ß-lactam antibiotics tivated by faecal substances (Veringa lactamases (Welling et al., 1987) in the ANTIBIOTIC RESISTANCE IN ENTEROBACTERIACEAE FROM HOSPITAL
PATIENTS
surgery (Datta, 1969) was performed.
Gram-negative bacilli as well as E. coli later Shaw and co-workers (1973) pub- found amongst E. coli, resistant strains either not treated or treated with tetra- excreted ampicillin resistant E. coli and 34% tetracycline resistant E. coli. A R-PLASMID TRANSFER IN VIVO
to receive R-plasmids in vivo is ex- clusively be due to selection of resistant habitat of E. coli is the human (and ani- mal) gut. In the intestines E. coli is fer of resistance plasmids. Whilst all the riaceae genera other than E. coli tend to tibiotic resistance markers to laboratory adapted to free-living existence. Plasmid den to Enterobacteriaceae (Zund and Lebek, 1981). It seems likely that a (Lacey, 1975). A rather recent study by well-adapted organism like E. coli is Platt and co-workers (1986) , reveals that in vivo transfer may occur in hospi- talized patients, particularly in E. coli such as Serratia (Platt and Sommerville, 1981) and Klebsiella (Smith, 1976) may sistance was not found (de Vies-Hos- confer sufficient genetic flexibility to re- pers et al., 1981), despite the fact that duce the benefits of plasmid carriage.
Bacteroides spp. are themselves capable not prevented (Dekker et al., 1981).
to be a rare event (Bawdon et al., treated group in a study by Anderson tion (Rozenberg-Arska et al., 1983).
amongst the bacteria of the faecal floraof a subject who had not received an- (Petrocheilon et al., 1976). Most other taking antibiotics, transfer is much more likely during antibiotic treatment with a plasmid transfer (Bawdon et al., 1982; LITERATURE
Anderson, J.D., Gillespie, W.A., and Rich- Burt, S.J., and Woods, D.R.: Evolution of transferable antibiotic resistance in coliform resistance transfer between enterobacteria in the human gastro-intestinal tract. J. Med.
Ball, P.: Antibiotic use as an inducer of resis- Datta, N.: Drug resistance and R factors in the tant urinary tract infections. Scand. J. In- and after admission to hospital. Brit. Med.
Bawdon, R.E., Crane, L.R., and Palchaudhuri, S.: Antibiotic resistance in anaerobic bacte- Dekker, A.W., Rozenberg-Arska, M., Sixma, ria: molecular biology and clinical aspects.
J.J., and Verhoef, J.: Prevention of infec- Berg, R.D., and Garlington, A.W.: Transloca- acute non-lymphocytic leukemia. Ann. Int.
tion of certain indigenous bacteria from the De Vies-Hospers, H.G., Sleijfer, D.Th., Mul- lymph nodes and other organs in a gnotobi- H.O., and van Saene, H.K.F.: Bacteriologi- cal aspects of selective decontamination of Berg, R.: Inhibition of translocation from the the digestive tract as a method of infection gastrointestinal tract by normal cecal flora prevention in granulocytopenic patients.
in gnotobiotic and antibiotic decontaminated Eickhoff, T.C.: Nosocomial respiratory tract ing prolonged tetracycline therapy. Antimi- infections: the gastrointestinal tract as a reservoir. In: New criteria for antimicrobial therapy: Maintenance of colonization resis- Platt, D.J., and Sommerville, J.S.: Serratia tance (Eds.: van der Waaij, D. and Verhoef, species isolated from patients in a general hospital. J. Hosp. Inf. 2, 341-348 (1981).
Platt, D.J., Chesham, J.S., and Kristinsson, Gardner, P., Smith, D.H., Beer, H., and Moel- K.G.: R-plasmid transfer in vivo: a prospec- lering, R.C.: Recovery of resistance (R) fac- tive study. J. Med. Microbiol. 21, 325-330 tors from a drug-free community. Lancet ii, Rozenberg-Arska, M., Dekker, A.W., and Ver- Gross, R.J., Gard, L.R., Trelfall, E.J., King, famethoxazole for prevention of infection in infantile enteropathogenic Escherichia coli strains isolated in the United Kingdom.
leukemia. Decrease in emergence of resis- tant bacteria. Infection 11, 167-169 (1983).
Hartley, C.L., and Richmond, M.H.: Antibi- Shaw, E.J., Datta, N., and Jones, G.: Effect of otic resistance and survival of E. coli in the stay in hospital and oral chemotherapy on alimentary tract. Brit. Med. J. iv, 71-74 antibiotic sensitivity of bowel coliforms. J.
Lacey, R.W.: A critical appraisal of the impor- Sleijfer, D.Th., Mulder, N.H., de Vries-Hos- tance of R-factors in the Enterobacteriaceae pers, H.G., Fidler, V., Nieweg, H.O., van in vivo. J. Antimicrob. Chemother. 1, 25- der Waaij, D., and van Saene, H.K.F.: In- fection prevention in granulocytopenic pa- Leading article: Transferable drug resistance.
tients by selective decontamination of the digestive tract. Eur. J. Cancer 16, 859-869 Leading article: Antibiotics and respiratory ill- Smith, H.W., and Halls, S.: Observations on Linton, K.B., Lee, P.A., Richmond, M.H., and infective drug resistance in Britain. Brit.
Gillespie, W.A.: Antibiotic resistance and transmittable R-factors in the intestinal col- Smith, H.W.: Mutants of Klebsiella pneumo- iform flora of healthy adults and children in niae resistant to several antibiotics. Nature an urban and rural community. J. Hyg. 70, van der Waaij, D., Berghuis-de Vries, J.M., and Lowbury, E.J.L., Babb, J.R., and Roe, E.: Lekkerkerk-van der Wees, J.E.C.: Coloniza- Clearance from a hospital of gram-negative tion resistance of the digestive tract in con- bacilli that transfer carbenicillin-resistance ventional and antibiotic-treated mice. J.
to Pseudomonas aeruginosa. Lancet ii, 941- van der Waaij, D., Berghuis-de Vries, J.M., and Moorhouse, E.C.: Transferable drug resistance Lekkerkerk-van der Wees, J.E.C.: Coloniza- in enterobacteria isolated from urban in- tion resistance of the digestive tract and the fants. Brit. Med. J. ii, 405-407 (1969).
spread of bacteria to the lymphatic organs in Nord, C.E., Kager, L., and Heimdahl, A.: Im- pact of antimicrobial agents on the gastroin- van der Waaij, D., and Berghuis-de Vries, J.M.: testinal microflora and the risk of infec- Selective elimination of Enterobacteriaceae tions. Am. J. Med. 76, 99-106 (1984).
species from the digestive tract in mice and Petrocheilon, V., Grinsted, J., and Richmond, monkeys. J. Hyg. 72, 205-211 (1974).
M.H.: R-plasmid transfer in vivo in the ab- van der Waaij, D.: Colonization resistance of sence of antibiotic selection pressure. An- the digestive tract as a major lead in the se- lection of antibiotics for therapy. In: New criteria for antimicrobial therapy: Mainte- Petrocheilon, V., Richmond, M.H., and Benett, nance of digestive tract colonization resis- P.M.: Spread of a single plasmid clone in tance (Eds.: van der Waaij, D., and Verhoef, an untreated individual from a person receiv- drug resistance in bacteria. Bact. Rev. 27, van der Waaij, D.: Colonization resistance of Welling, G.W., Groen, G., Welling-Wester, the digestive tract; clinical consequences and implications. J. Antimicrob. Chemother.
Waaij, D.: Enzymatic inactivation of aztre- van der Waaij, D., de Vries-Hospers, H.G., and healthy volunteers. Infection 15, 188-191 Welling, G.W.: The influence of antibiotics Williams Smith, H.: Survival of orally admin- Chemother. 18 suppl. C, 155-158 (1986).
istered E. coli in the alimentary tract of Veringa, E.M., and van der Waaij, D.: Biologi- cal inactivation by faeces of antimicrobial Zund, P., and Lebek, G: Generation time-pro- drugs applicable in selective decontamina- longing R-plasmids: correlation between in- tion of the digestive tract. J. Antimicrob.
crease in the generation time of Escherichia coli caused by R-plasmids and their molecu- Watanabe, T.: Infective heredity of multiple

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