Journal of Chemotherapy
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
Effect of a Broad-Spectrum Cephalosporin on the Oral and Intestinal Microflora in Patients Undergoing Colorectal Surgery V. Cavallaro, V. Catania, R. Bonaccorso, S. Mazzone, A. Speciale, R. Di Marco, G. Blandino & F. Caccamo To cite this article: V. Cavallaro, V. Catania, R. Bonaccorso, S. Mazzone, A. Speciale, R. Di Marco, G. Blandino & F. Caccamo (1992) Effect of a Broad-Spectrum Cephalosporin on the Oral and Intestinal Microflora in Patients Undergoing Colorectal Surgery, Journal of Chemotherapy, 4:2, 82-87, DOI: 10.1080/1120009X.1992.11739145 To link to this article: http://dx.doi.org/10.1080/1120009X.1992.11739145
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Journal of Chemotherapy
Effect of a Broad-Spectrum Cephalosporin on the Oral and Intestinal Microflora in Patients Undergoing Colorectal Surgery
Vol. 4 - n. 2 (82-87) - 1992
enterobacteria were eliminated or strongly suppressed. Only minor changes in the number of aerobic gram-positive bacteria were observed, and the anaerobic intestinal flora showed only minor alterations. On day 28 the intestinal flora were normalized in all respects. No new colonizing microorganisms were isolated during the investigation period and no colonization with ceftriaxone-resistant bacteria was observed. No postoperative infection occurred and no adverse effects were registered. Key Words: short-term prophylaxis, microbial flora, saliva, feces.
y.
CAVALLARO* - V. CATANIA * R. BONACCORSO * - S. MAZZONE * A. SPECIALE ** - R. DI MARCO ** G. BLANDINO ** - F. CACCAMO **
Summary --------------------------------The influence of ceftriaxone on oral and intestinal flora was investigated in 10 patients undergoing colorectal surgery. Ceftriaxone was given intravenously in one 2g dose before anesthesia. Saliva and feces samples were collected and analyzed on day 0, 3, 5, 14 and 28 after drug administration. All specimens were cultured quantitatively for aerobic and anaerobic microorganisms; representative colonies of each morphologic type of organism cultured were identified. The oral aerobic flora was somewhat affected by the administration of ceftriaxone. In all patients the number of Streptococci, Staphylococci and Neisseria decreased during the 5 days after ceftriaxone administration. No significant changes in the number of anaerobic commensal occurred. The oral microflora of all patients after 14 days had returned to normal. The aerobic fecal flora was considerably affected: in all patients
* lstituto eli I Clinica Chirurgica Generale e Terapia Chirurgica, Universita eli Catania, Italy. ** lstituto eli Microbiologia, Universita eli Catania, Italy. Correspondence: Prof. V. Cavallaro, I Clinica Chirurgica Generale e Terapia Chirurgica, Policlinico, Via S. Sofia, 95125 Catania, Italy. © Edizioni Riviste Scientifiche - Firenze
INTRODUCTION
Treatment with antimicrobial agents can induce changes in the oral and gastrointestinal microflora. In most cases this influence is deleterious to the patient because suppression of the indigenous microflora often permits overgrowth of potentially pathogenic microorganisms and can cause septic conditions, stomatitis, diarrhea or colitis 1 ' 2 ' 3 ' 4 • Moreover the anaerobic flora has an inhibitory effect on potentially pathogenic aerobic microorganisms and may act as a resistance factor against new colonization 5 • Infections are responsible for the majority of postoperative surgical complications. The high risk of infection following colorectal surgery is reduced by the administration of prophylactic antimicrobials directed against both aerobic and anaerobic microorganisms 6 • 7 • Sometimes, however, the administration of antibiotics alters the aerobic-anaerobic balance of endogenous microflora, and subsequent overgrowth or new colonization with antibiotic resistant bacteria or fungi may occur 8 • 9 • Ceftriaxone, a broad spectrum cephalosporin, has been ISSN 1120-009X
EFFECT OF A BROAD-SPECTRUM CEPHALOSPORIN ON . THE ORAL AND INTESTINAL MICROFLORA, ETC .
shown to be active against most microorganisms involved in intra-abdominal sepsis and to have good distribution and penetration into many body tissues 10 • The purpose of this study was to obtain data about the effect of short-term prophylaxis with ceftriaxone on the changes in throat and colon microflora and the emergence of antibiotic-resistant strains in patients undergoing colorectal surgery.
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PATIENTS AND METHODS
Patients Ten female patients, between 60 and 80 years old (median age 67.3 years) undergoing colorectal surgery were included in this investigation. Groups were well matched for sex (female), type of disease (malignant tumors), type and duration of surgery (approximately 4 hours) and underlying pathology. Four subjects were treated with abdominalperineal rectal extirpation, four with right hemicolectomy and two with left hemicolectomy. All patients were prepared with one liter of mannitol administered per os and mechanical bowel preparation with two enemas of one liter of H20.
Ceftriaxone administration One dose administered esia. No other administered
of 2 g of ceftriaxone (Roche) was intravenously just before anesthoral or systemic antibiotics were during the study period.
83
Microbiological procedures One milliliter of saliva was suspended in prereduced peptone-yeast extract medium, diluted and duplicate samples were inoculated on different selective and non-selective media 11 • 12 • 13 • 14 • The aerobic agar plates were incubated for 24 hat 37° C and the anaerobic plates were incubated for 48 h at 37° C in anaerobic jars (Gas Pack, BBL Microbiology Systems). Organisms were indentified by the methods of Edwards and Ewing 15 and Cowan and Steel 11 • Anaerobic organisms were identified according to established methods 13 • All manipulations of the anaerobic media were performed in an anaerobic chamber (Coy, Ann Arbor, MI) under a 90% (V/V) nitrogen and 10% (V/V) hydrogen atmosphere. A 1g sample of feces was homogenized in 9 ml of prereduced peptone-yeast extract medium. Tenfold serial dilutions were made to a dilution of 10 - 8 • Duplicate samples of 0.1 ml of the appropriate dilutions were inoculated on different non-selective and selective media 11 • 12 • 13 • 14 • Incubation and identification were performed as previously described for saliva samples. Representative colonies of each morphologic type of organism cultured were identified. Only the organisms that were isolated from both saliva and feces samples obtained before drug administration were considered in the analysis. Persistent organisms were defined as those that were isolated from samples obtained before the antibiotic perioperative prophylaxis and from the specimens collected at the end of drug administration and at the follow-up.
RESULTS
Sampling procedures
Effect of ceftriaxone on the oral flora
Saliva and feces specimens were taken for culture the day before the operation (day 0), then on day 3 and day 5. Follow-up samples were collected on day 14 and day 28. The specimens were collected in the morning in sterile plastic containers; the containers were placed in ice chests and transported to the laboratory as soon as possible. The time lapse between collection and plating was usually one hour.
The impact of a single dose of ceftriaxone on the aerobic oral flora is shown in Figure 1. The number of Streptococci decreased during the first 5 days from approximately 1 X 10 7 - 1 X 10 8 to 1 X 10 4 • The number of Staphylococci, Micrococci and Neisseria was also significantly changed during the observation period in all patients. The aerobic flora slowly increased to the same level as before ceftriaxon_e administration.
84
V. CAVALLARO - V. CATANIA - R. BONACCORSO - S. MAZZONE,
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Downloaded by [Australian Catholic University] at 12:52 26 August 2017
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Figure 1 - Effect of one dose of ceftriaxone (2g IV) on the aerobic oral flora of 10 patients.
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Figure 2 - Effect of one dose of ceftriaxone (2~ IV) on the anaerobic oral ora of 10 patients .
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85
EFFECT OF A BROAD-SPECTRUM CEPHALOSPORIN ON THE ORAL AND INTESTINAL MICROFLORA, ETC.
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Log number of bocteri o1 grom
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Figure 3 - Effect of one dose of ceftriaxone (2g IV) on the ~erobic fecal flora of 10 patIents.
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The anaerobic oral flora were not markedly affected by the administration of ceftriaxone (Figure 2). Two weeks after withdrawal of ceftriaxone, the oral microflora had returned to normal levels in all surgical patients.
EHect of ceftriaxone on the intestinal flora The aerobic colon microflora were selectively inhibited by the ceftriaxone administration (Figure 3). During the first 5 days after drug administration, a marked decrease in the number of Enterobacteria to undetectable levels was observed in 7 patients. A rapid increase in the number of Enterobacteria to the same level as before antibiotic administration was noted after 2 weeks. Enterococci, mainly Streptococcus faecalis that were initially cultured, persisted after drug administration. Not surprisingly, in view of the lack of activity of cephalosporins against Enterococci, these increased in most patients. The aerobic
..• •
..
ST APHVLOCOCC 1-STREPTOCOCC I
..•..•. •
.. ..
•• ••• •
colon microflora became normal after 14 days in all patients . The anaerobic flora showed only minor alterations (Figure 4). The number of anaerobic bacteria decreased from the first to the fifth day (> 2 logio) and returned to the initial number after 14 days in all subjects. No new colonizing microorganism was isolated during the investigation period.
Clincical findings No postoperative infection occurred and no adverse effects were registered; only in one case was diarrhea observed. DISCUSSION
The impact of ceftriaxone on the flora of the lower gastrointestinal tract is not surprising since a substantial proportion of this drug is excreted via the biliary tract 14 • Enterobacteria, in particular Escherichia coli, showed a signifi-
86
V. CAVALLARO - V. CATANIA - R. BONACCORSO - S. MAZZONE,
Log number of bocteri 111 grem
.. ............
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Downloaded by [Australian Catholic University] at 12:52 26 August 2017
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Figure 4 -Effect of one dose of ceftriaxone (2g IV) on the anaerobic fecal flora of 10 patients.
ANAEROBIC COCCI
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cant decrease and no ceftriaxone resistant strains were detected. Only Enterococci, especially 5. faecalis, proliferated; this microorganism, however, is considered to be of a low pathogenicity in abdominal infections. Ceftriaxone had a less marked effect on the oral flora, probably because this body site is exposed to lower drug concentrations and harbors a different microbial population. After the administration period, both the oral and colonic microflora quickly returned to normal. The microbiologic effect of administration was favorable. In fact a single dose of 2 g IV perioperatively does not markedly alter the colon microflora and no colonization with new microorganisms was observed. On the basis of these findings, a single administration of ceftriaxone, just before surgery,
..........
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was sufficient to prevent postoperative infection in colo rectal surgery. Furthermore, as proposed by Nord et al., 8 • 9 the risk of superinfection from nosocomial microorganisms as a consequence of substantial alteration in microbial flora is not apparent. A comparison between ceftriaxone and other agents recommended for prophylaxis m colorectal surgery should be made. AcKNOWLEDGEMENT N° 91.00115.41 National Research Council (CNR) - Targeted Project "Prevention and Control Disease Factors"; Subproject "Cause of Infectious Disease".
REFERENCES ' Bodey GP. Epidemiological studies of Pseudomonas species in patients with leukemia. Am J Sci 1970; 260: 82-89 . 1 Bodey GP, Rosemburg B, Valdivieso M, Bolavir R.
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EFFECT OF A BROAD-SPECTRUM CEPHALOSPORIN ON THE ORAL AND INTESTINAL MICROFLORA, ETC.
Effect of systemic antimicrobial prophylaxis on microbial flora. Antimicrob Agents Chemother 1982; 21 : 367-372. 'Johanson WG Jr, Pierce AK, Sanford JP, Thomas GP. Nosocomial respiratory infections with gram-negative bacilli: the significance of colonization of respiratory tract. Ann Intern Med 1972; 77 : 701-706. ' Nord CE, Heimdahl A, Kanger L. Antimicrobial induced alterations of the human oropharyngeal and intestinal microflora. Scand J Infect Dis 1986; 49 (Suppl): 64-72 . ' Gorbach SL. Function of the normal human rnicroflora. Scand J Infect Dis 1986; 49 (Suppl) : 17-30. 'Polk BF. Antimicrobial prophylaxis to prevent mixed bacterial infections. J Antimicrob Chemother 1981; 8: 115129. 7 Kager L, Ljungdahl I, Malmberg AS, Nord CE, Pieper R, Dahlgren P. Antibiotic prophylaxis with cefoxitin in colorectal surgery. Ann Surg 1981; 193 : 277-282 . • Nord CE, Heimdahl A, Kager L, Malmberg AS. The impact of different antimicrobial agents on the normal gastrointestinal microflora of humans. Rev Infect Dis 1984; 6(Suppl. 1): 270-275 . • Nord CE, Kager L, Heimdahl A. Impact of antirnicrob-
87
ial agents on the gastrointestinal rnicroflora and the risk of infection. Am J Med 1984; 76: 99-106. 0 ' Arvidsson A, Alvan G, Augetin B, Barga 0, Nord CE . Ceftriaxone: renal and biliary excretion and effect on the colon rnicroflora. J Antirnicrob Chemother 1982; 10: 207215 . " Cowan ST, Steel KJ. Manual for the identification of medical bacteria. London: Cambridge University Press, 1965 . 12 Heimdahl A, Nord CE . Effect of phenoxymethylpenicillin and clindamycin on the oral, throat and faecal rnicroflora of man. Scand J Infect Dis 1979; 11: 232-242 . "Heidemann LV, Cato EP, Moore WEC . Anaerobe laboratory manual. Blacksburg, Va: Virginia Polytechnic Institute and State University, 1977. "Sutter VL, Vargo VL, Finegold SM . Wadsworth Anaerobic Bacteriology Manual. Los Angeles, University of California, 1975 . " Edwards PR, Ewing WH. Identification of Enterobacteriaceae. Minneapolis: Burgess, 1964. " Erisson HM, Sherris JC. Antibiotic sensitivity testing. Report of an international collaborative study. Acta Pathol Microbial Scand 1971; (Suppl.) 217 : 1-90.
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
Effect of a Broad-Spectrum Cephalosporin on the Oral and Intestinal Microflora in Patients Undergoing Colorectal Surgery V. Cavallaro, V. Catania, R. Bonaccorso, S. Mazzone, A. Speciale, R. Di Marco, G. Blandino & F. Caccamo To cite this article: V. Cavallaro, V. Catania, R. Bonaccorso, S. Mazzone, A. Speciale, R. Di Marco, G. Blandino & F. Caccamo (1992) Effect of a Broad-Spectrum Cephalosporin on the Oral and Intestinal Microflora in Patients Undergoing Colorectal Surgery, Journal of Chemotherapy, 4:2, 82-87, DOI: 10.1080/1120009X.1992.11739145 To link to this article: http://dx.doi.org/10.1080/1120009X.1992.11739145
Published online: 15 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 10 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yjoc20 Download by: [Australian Catholic University]
Date: 26 August 2017, At: 12:52
Downloaded by [Australian Catholic University] at 12:52 26 August 2017
Journal of Chemotherapy
Effect of a Broad-Spectrum Cephalosporin on the Oral and Intestinal Microflora in Patients Undergoing Colorectal Surgery
Vol. 4 - n. 2 (82-87) - 1992
enterobacteria were eliminated or strongly suppressed. Only minor changes in the number of aerobic gram-positive bacteria were observed, and the anaerobic intestinal flora showed only minor alterations. On day 28 the intestinal flora were normalized in all respects. No new colonizing microorganisms were isolated during the investigation period and no colonization with ceftriaxone-resistant bacteria was observed. No postoperative infection occurred and no adverse effects were registered. Key Words: short-term prophylaxis, microbial flora, saliva, feces.
y.
CAVALLARO* - V. CATANIA * R. BONACCORSO * - S. MAZZONE * A. SPECIALE ** - R. DI MARCO ** G. BLANDINO ** - F. CACCAMO **
Summary --------------------------------The influence of ceftriaxone on oral and intestinal flora was investigated in 10 patients undergoing colorectal surgery. Ceftriaxone was given intravenously in one 2g dose before anesthesia. Saliva and feces samples were collected and analyzed on day 0, 3, 5, 14 and 28 after drug administration. All specimens were cultured quantitatively for aerobic and anaerobic microorganisms; representative colonies of each morphologic type of organism cultured were identified. The oral aerobic flora was somewhat affected by the administration of ceftriaxone. In all patients the number of Streptococci, Staphylococci and Neisseria decreased during the 5 days after ceftriaxone administration. No significant changes in the number of anaerobic commensal occurred. The oral microflora of all patients after 14 days had returned to normal. The aerobic fecal flora was considerably affected: in all patients
* lstituto eli I Clinica Chirurgica Generale e Terapia Chirurgica, Universita eli Catania, Italy. ** lstituto eli Microbiologia, Universita eli Catania, Italy. Correspondence: Prof. V. Cavallaro, I Clinica Chirurgica Generale e Terapia Chirurgica, Policlinico, Via S. Sofia, 95125 Catania, Italy. © Edizioni Riviste Scientifiche - Firenze
INTRODUCTION
Treatment with antimicrobial agents can induce changes in the oral and gastrointestinal microflora. In most cases this influence is deleterious to the patient because suppression of the indigenous microflora often permits overgrowth of potentially pathogenic microorganisms and can cause septic conditions, stomatitis, diarrhea or colitis 1 ' 2 ' 3 ' 4 • Moreover the anaerobic flora has an inhibitory effect on potentially pathogenic aerobic microorganisms and may act as a resistance factor against new colonization 5 • Infections are responsible for the majority of postoperative surgical complications. The high risk of infection following colorectal surgery is reduced by the administration of prophylactic antimicrobials directed against both aerobic and anaerobic microorganisms 6 • 7 • Sometimes, however, the administration of antibiotics alters the aerobic-anaerobic balance of endogenous microflora, and subsequent overgrowth or new colonization with antibiotic resistant bacteria or fungi may occur 8 • 9 • Ceftriaxone, a broad spectrum cephalosporin, has been ISSN 1120-009X
EFFECT OF A BROAD-SPECTRUM CEPHALOSPORIN ON . THE ORAL AND INTESTINAL MICROFLORA, ETC .
shown to be active against most microorganisms involved in intra-abdominal sepsis and to have good distribution and penetration into many body tissues 10 • The purpose of this study was to obtain data about the effect of short-term prophylaxis with ceftriaxone on the changes in throat and colon microflora and the emergence of antibiotic-resistant strains in patients undergoing colorectal surgery.
Downloaded by [Australian Catholic University] at 12:52 26 August 2017
PATIENTS AND METHODS
Patients Ten female patients, between 60 and 80 years old (median age 67.3 years) undergoing colorectal surgery were included in this investigation. Groups were well matched for sex (female), type of disease (malignant tumors), type and duration of surgery (approximately 4 hours) and underlying pathology. Four subjects were treated with abdominalperineal rectal extirpation, four with right hemicolectomy and two with left hemicolectomy. All patients were prepared with one liter of mannitol administered per os and mechanical bowel preparation with two enemas of one liter of H20.
Ceftriaxone administration One dose administered esia. No other administered
of 2 g of ceftriaxone (Roche) was intravenously just before anesthoral or systemic antibiotics were during the study period.
83
Microbiological procedures One milliliter of saliva was suspended in prereduced peptone-yeast extract medium, diluted and duplicate samples were inoculated on different selective and non-selective media 11 • 12 • 13 • 14 • The aerobic agar plates were incubated for 24 hat 37° C and the anaerobic plates were incubated for 48 h at 37° C in anaerobic jars (Gas Pack, BBL Microbiology Systems). Organisms were indentified by the methods of Edwards and Ewing 15 and Cowan and Steel 11 • Anaerobic organisms were identified according to established methods 13 • All manipulations of the anaerobic media were performed in an anaerobic chamber (Coy, Ann Arbor, MI) under a 90% (V/V) nitrogen and 10% (V/V) hydrogen atmosphere. A 1g sample of feces was homogenized in 9 ml of prereduced peptone-yeast extract medium. Tenfold serial dilutions were made to a dilution of 10 - 8 • Duplicate samples of 0.1 ml of the appropriate dilutions were inoculated on different non-selective and selective media 11 • 12 • 13 • 14 • Incubation and identification were performed as previously described for saliva samples. Representative colonies of each morphologic type of organism cultured were identified. Only the organisms that were isolated from both saliva and feces samples obtained before drug administration were considered in the analysis. Persistent organisms were defined as those that were isolated from samples obtained before the antibiotic perioperative prophylaxis and from the specimens collected at the end of drug administration and at the follow-up.
RESULTS
Sampling procedures
Effect of ceftriaxone on the oral flora
Saliva and feces specimens were taken for culture the day before the operation (day 0), then on day 3 and day 5. Follow-up samples were collected on day 14 and day 28. The specimens were collected in the morning in sterile plastic containers; the containers were placed in ice chests and transported to the laboratory as soon as possible. The time lapse between collection and plating was usually one hour.
The impact of a single dose of ceftriaxone on the aerobic oral flora is shown in Figure 1. The number of Streptococci decreased during the first 5 days from approximately 1 X 10 7 - 1 X 10 8 to 1 X 10 4 • The number of Staphylococci, Micrococci and Neisseria was also significantly changed during the observation period in all patients. The aerobic flora slowly increased to the same level as before ceftriaxon_e administration.
84
V. CAVALLARO - V. CATANIA - R. BONACCORSO - S. MAZZONE,
Log number of bocterio/ ml
•• ........ ......
8 7
s 5 4 3 2 1
.. ......
..
.. ........ ....
•• ••• •
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..... ......... •
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..
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......•
.• •• .... .. •
et alii
..••..... ....
..•• .••...•..
.... ... .. ...
............ .......
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0
7 6
....... .....
Downloaded by [Australian Catholic University] at 12:52 26 August 2017
~
4 3
Figure 1 - Effect of one dose of ceftriaxone (2g IV) on the aerobic oral flora of 10 patients.
2 1 0
Doys
Log number of bccter1 o1 ml
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Figure 2 - Effect of one dose of ceftriaxone (2~ IV) on the anaerobic oral ora of 10 patients .
......... ••• :
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85
EFFECT OF A BROAD-SPECTRUM CEPHALOSPORIN ON THE ORAL AND INTESTINAL MICROFLORA, ETC.
Downloaded by [Australian Catholic University] at 12:52 26 August 2017
Log number of bocteri o1 grom
....••z ...•
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Figure 3 - Effect of one dose of ceftriaxone (2g IV) on the ~erobic fecal flora of 10 patIents.
..• .. ••••••• ..•
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The anaerobic oral flora were not markedly affected by the administration of ceftriaxone (Figure 2). Two weeks after withdrawal of ceftriaxone, the oral microflora had returned to normal levels in all surgical patients.
EHect of ceftriaxone on the intestinal flora The aerobic colon microflora were selectively inhibited by the ceftriaxone administration (Figure 3). During the first 5 days after drug administration, a marked decrease in the number of Enterobacteria to undetectable levels was observed in 7 patients. A rapid increase in the number of Enterobacteria to the same level as before antibiotic administration was noted after 2 weeks. Enterococci, mainly Streptococcus faecalis that were initially cultured, persisted after drug administration. Not surprisingly, in view of the lack of activity of cephalosporins against Enterococci, these increased in most patients. The aerobic
..• •
..
ST APHVLOCOCC 1-STREPTOCOCC I
..•..•. •
.. ..
•• ••• •
colon microflora became normal after 14 days in all patients . The anaerobic flora showed only minor alterations (Figure 4). The number of anaerobic bacteria decreased from the first to the fifth day (> 2 logio) and returned to the initial number after 14 days in all subjects. No new colonizing microorganism was isolated during the investigation period.
Clincical findings No postoperative infection occurred and no adverse effects were registered; only in one case was diarrhea observed. DISCUSSION
The impact of ceftriaxone on the flora of the lower gastrointestinal tract is not surprising since a substantial proportion of this drug is excreted via the biliary tract 14 • Enterobacteria, in particular Escherichia coli, showed a signifi-
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V. CAVALLARO - V. CATANIA - R. BONACCORSO - S. MAZZONE,
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cant decrease and no ceftriaxone resistant strains were detected. Only Enterococci, especially 5. faecalis, proliferated; this microorganism, however, is considered to be of a low pathogenicity in abdominal infections. Ceftriaxone had a less marked effect on the oral flora, probably because this body site is exposed to lower drug concentrations and harbors a different microbial population. After the administration period, both the oral and colonic microflora quickly returned to normal. The microbiologic effect of administration was favorable. In fact a single dose of 2 g IV perioperatively does not markedly alter the colon microflora and no colonization with new microorganisms was observed. On the basis of these findings, a single administration of ceftriaxone, just before surgery,
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was sufficient to prevent postoperative infection in colo rectal surgery. Furthermore, as proposed by Nord et al., 8 • 9 the risk of superinfection from nosocomial microorganisms as a consequence of substantial alteration in microbial flora is not apparent. A comparison between ceftriaxone and other agents recommended for prophylaxis m colorectal surgery should be made. AcKNOWLEDGEMENT N° 91.00115.41 National Research Council (CNR) - Targeted Project "Prevention and Control Disease Factors"; Subproject "Cause of Infectious Disease".
REFERENCES ' Bodey GP. Epidemiological studies of Pseudomonas species in patients with leukemia. Am J Sci 1970; 260: 82-89 . 1 Bodey GP, Rosemburg B, Valdivieso M, Bolavir R.
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EFFECT OF A BROAD-SPECTRUM CEPHALOSPORIN ON THE ORAL AND INTESTINAL MICROFLORA, ETC.
Effect of systemic antimicrobial prophylaxis on microbial flora. Antimicrob Agents Chemother 1982; 21 : 367-372. 'Johanson WG Jr, Pierce AK, Sanford JP, Thomas GP. Nosocomial respiratory infections with gram-negative bacilli: the significance of colonization of respiratory tract. Ann Intern Med 1972; 77 : 701-706. ' Nord CE, Heimdahl A, Kanger L. Antimicrobial induced alterations of the human oropharyngeal and intestinal microflora. Scand J Infect Dis 1986; 49 (Suppl): 64-72 . ' Gorbach SL. Function of the normal human rnicroflora. Scand J Infect Dis 1986; 49 (Suppl) : 17-30. 'Polk BF. Antimicrobial prophylaxis to prevent mixed bacterial infections. J Antimicrob Chemother 1981; 8: 115129. 7 Kager L, Ljungdahl I, Malmberg AS, Nord CE, Pieper R, Dahlgren P. Antibiotic prophylaxis with cefoxitin in colorectal surgery. Ann Surg 1981; 193 : 277-282 . • Nord CE, Heimdahl A, Kager L, Malmberg AS. The impact of different antimicrobial agents on the normal gastrointestinal microflora of humans. Rev Infect Dis 1984; 6(Suppl. 1): 270-275 . • Nord CE, Kager L, Heimdahl A. Impact of antirnicrob-
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ial agents on the gastrointestinal rnicroflora and the risk of infection. Am J Med 1984; 76: 99-106. 0 ' Arvidsson A, Alvan G, Augetin B, Barga 0, Nord CE . Ceftriaxone: renal and biliary excretion and effect on the colon rnicroflora. J Antirnicrob Chemother 1982; 10: 207215 . " Cowan ST, Steel KJ. Manual for the identification of medical bacteria. London: Cambridge University Press, 1965 . 12 Heimdahl A, Nord CE . Effect of phenoxymethylpenicillin and clindamycin on the oral, throat and faecal rnicroflora of man. Scand J Infect Dis 1979; 11: 232-242 . "Heidemann LV, Cato EP, Moore WEC . Anaerobe laboratory manual. Blacksburg, Va: Virginia Polytechnic Institute and State University, 1977. "Sutter VL, Vargo VL, Finegold SM . Wadsworth Anaerobic Bacteriology Manual. Los Angeles, University of California, 1975 . " Edwards PR, Ewing WH. Identification of Enterobacteriaceae. Minneapolis: Burgess, 1964. " Erisson HM, Sherris JC. Antibiotic sensitivity testing. Report of an international collaborative study. Acta Pathol Microbial Scand 1971; (Suppl.) 217 : 1-90.
