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The effect of chlorhexidine mouth rinses on oral Candida in a group of leukemic patients
The effect of chlorhexidine mouth rinses on oral Candida in a group of leukemic patients
DEPARTRIENT
OF
BIOLOGY, SCHOOL
RARIBAZRZ OF
ORAL
ASD
1\IEDICAI,
JIAXILLO-FACIAL CENTER
AND
SURGERY,
LABORATORY
DEI’ARThIE:NT
OF
OF
ORLiL
MICROBIOLO(~~,
3IEDICINE
Eighteen leukemic patients were examined for the presence the oral cavity. Fifteen patients were found to be Candida patients were put on a chlorhexidine mouth rinse regimen. was clearly fungicidal in vitro, no decrease in Candida titer mouth rinse. The ineffectiveness of the drug in viro might location of Candida organisms in the oral mucosa.
of Can&& albicnns in “cvlrriers.” Nine of the Although chlorllexidine was obtained with tllv hc due to the specific
C
uudida, nlbictx~s, usually a saprophy-te in the oral cavities of many healthy persons, sometimes causes various fungal infections. Oral candidiasis, usually initiated by local trauma, I-3 is being treated successfully. However, widespread infclctions of Candida in the gastrointestinal and respiratory systems present major therapeutic problems and often may bc fatal. They may occur as a corn plivation in patients irradiated for malignant lesions of the head and neck’ and in leukemic patients who receive irnmurlosul)Pressivc therapy.“, ” Since the prcs(:nw of C’n)ldidn crlbicw~s in the oral cavity appears to lx the starting point of infection, it is desirable to detect Candida “carriers” among these patients and to rctluce the danger of widespread infections by means of a specific prophylactic agcllt. Chlorhexidine is one of the therapeutic agents suggest,edfor oral candidiasis.+’ &sides its well-known activity against dental plaque in viva, it was shown to cure mouth thrush in seriously diseased children” and denture stomatitis in edentulous patients.8 The fungicidal effect of chlorhesidine in vitro has been recently demonstrated.” The purpose of the present stutlp was to determine the incidence of oral 201
MATERIALS
AND
METHODS
pcrimcntaI trch;ltnrcsllt with 0.2 l)(‘r cent c~hIorhexidinc~mouth rinses. The patients were instructetl to rinse for 1 minute>with 10 ml. of solution. They rind t~wicc daily for the first wwk, then st,oplwtl rinsing for 1 week, and started again four times per day for another week. Sali\-ary samples ww dlccttd 1 wek befow t,rcatmcnt and sew1~~1times tluring the c~sperimcnt. On the first, (lay it WEH COGIcctM just brfow, imnl~Xli;~tc~l~~ after, aiitl 30 minutes I’ollowing the first riirw. Saliva was the11wllwtotl onw :I ILcd~ for 4 wcel~s. 7%~ candida titer was ostahlishctl for ever,v sample. The cffcct of vhlorhcsidinv on (‘~r~did~ trlbicco~swas testetl in vitro. ~Ihlorhesicline glwoiiatc~ at different wncentrations was a~ltletl to a solution of Cnxdid0 trlhictr~rs (5 s 1W per milliliter). Samples of 0.1 ml. wrt taken at, l-minute illtcrrals for 3 niinulw and analyxctl as abo\-cx.
RESULTS
There was no clinical evitlww oi’ (‘andida in the oral cavity of the eighteen I)iiticlnts suffering from chronic. leukemia. II OWPLY~~, in fifteen of thcxpatients the salivary titers OF (‘alltlitlil i*aiig!.cylbct\\ecln 10” all(l 10’ ]x’r milliliter, ancl thPSc patients were clcfillcd as “( liHltlitl:l c~arricrs.“ ‘I%(~ (‘;llldicli~ tikrs of Iiinc I)i~ti(~lliS who i~inscvl \vith c~hlorht~siclinearc presentcd in Table J. No significant (Icc~rc:awill titctr was found in any of the paticnts. Al)art from a slight taste tiisordcr in son~e,thv patients did not complain of ari?’ sidt effects (luring the rilisiilg lwriod. The action ot‘ c~hlorhcsiclinc~OII (‘;tntlitli~ in vitro is demonstrated in Table II.
I. The titer of Candida in saliva during (microorganisms per milliliter)
Table
PaIiWll ?YO
I
3 5 4 5 6 7 h Y
Sample 0
I
2
/
chlorhexidine
rinses
No.
3
4
5
6
7
I X10’
I.1 x 10’
6.5 x IO5
4 3.3 I.5 2 1.5 5 3 I.5
37 2 3 5 5 1 I
32 8 5 5
x103 Xl02 x103 x103
41 xXl03IO”
45x xro210’
61.5 x10’ x IO’
3x 6X
1 XIOS 3x lo3
3 Go4 3x I03
2 X104 2x104
I Xl03 -
-
6 8
x102 Xl02
4 x102 4x 103
2x
2
5 x102 -
5x
Xl02 x IO’ x 103 Xl03 x IO’ x103 x103 x IO”
x10* X10’ Xl03 X10’ x103 x102 x103 x103
4
1
103
x103
x103
I x 103 I03 IO2
3 hl03
-
10”
Samples (time of collection) : 0 - One week before rinsing. I - Immediately before rinsing. 2 - 30 minutes following rinsing. :j - After one week of rinsing (x2). 1 - After one week without rinsing. .i After another week of rinsing (x4). pi - After another week without rinsing. 7 - After one rinse with placebo.
The in vitro effect of chlorhexidine per milliliter)
Table
C‘hlorhexidine concentration (ALglml. I 200 400 500 600 700 800
Table
on Catldida albicans
II.
Time 0 5x 5x 5x 5x 5x 5X
The influence
Ill.
of incubation
I lo7 IO7 IO7 IO7 IO7 107
I x 5x 6X 2x I x
IO8 105 IO3 102 10’
Time
of incubation
0
I
I
1 x 105
1 x 102
23
6x 5x
5x 1 x 10’ 102
10” lo6
(minures) 2
3
8X 10’ 5x IO’ 1 x IO” 0 i
I x IO’ 5x I03 I x IO’ 0 0 0
0
of saliva on the effectiveness
Sanlnle x;.
(microorganisms
of chlorhexidine (minutes) 2
3 0
22x x0103 102
:
Chlorhexidine gluconate in very low concentrations lowered the titer of Candida considerably. A solution of 600 pg/ml brought the fungal titer to zero within 2 minutes. At 800 pg/ml., 1 minute was enough to sterilize the solution. The influence of saliva on the effectiveness of chlorhexidine is demonstrated in Table III. Sterilization of all three samples was achieved within 3 minutes. It is evident that saliva did not inhibit the fungi&la1 effect of chlorhexidine. Table IV shows the change in titer of Candida following a single mouth rinse. Four “carriers” had an initial titer ranging between 2.5 x 102/ml. and 7.5 x
t I4hjcc.f I
0 4
Xl03
1
I
,
0
2.5 x 103
? 2x
i IO3
I 1
4 7x
IO3
.: 3
YIO”
udablished, It istherefore prold~lc thatCandida organisms arecontinuonsly rclcascclfrom the oral mucosa where they are not effectively exposedto the drug. Whereas chlorhcsidine is very effective against dental plaque because of its absorption to the tceth,‘“~ I4 it was practically ineffective in Candida “carriers.” Its moclr~ of action on the fungal cells will be sul)jectctl to further investigations. \Vr would like to thank the staff their 11~11) in selecting and examining :lnc’,l.
of the Hematology the patients and
Department Mrs. A. Hxrari
and Dr. 811. Grinman for for her technical assist-
REFERENCES 1. .Jcnkins, 2. 3. 4.
.i. 6.
nlbicms, ~Iasrlla, Hilastin Olsen Scani (‘hen, Cancer Mirsky, Igig. langslct,
IV. M. M., T~IO~RS, H. C., and Mason, 1). I<. : Oral Infections With Cantlidn Hrott. Med. J. 18: 192-200, 1973. H. P., Holan, Ch.T., and Laney, W. R.: The Prevention of Growth of Candida on 390 Soft Liner for I)entures, J. Prosthet. Dent. 33: 250-257, 1975. 1.: Denture Stomutitis: Occurrence and I)i.strilmtion of Fungi, Acta Odontol. 32: 329-331 1074 . . T. I’., and ‘<\‘el,ster, J. 11.: Oral Monilia Study on Patients With Head and Neck DuringRadiotherapy, Cancer 34: 246-249, 197< H. R., and Cuttner, J. : Fungal Infection in ;\cute Leukemia, Cancer 30: 348-352,
et al. : Cl~lorhesidinc~ Treatment of Oral Canclidiasis in 8criously Diseased Pardiatr. Sand. 63: X09-81 1, 1971. J. Clin. Periodont,ol. 1: 1X1-152, 1974. C~j~rmo, P. : Chlorlrrsidinc~ in J)rntal Practice, J~udt~-.Jiirgc,nsnl, E., and Liie, If. : Cklorhesidine as :I Hrnture Disinfectant in the Treatment of I)rnture Rtomatitis, Stand. .J. Hcwt. Res. 80: 137-464, 1972. I?crtlicevsky, l., et al. : Tlic Effect of (:hlorhexidine on ~‘crndidn crlbitnns In Vitro. (In prcparation.) Rerdiwvsky, J., et al. : d Strip ‘lost for Hetectirrg Candida in tile Oral Cal-ity, O~.\I) StTt:o. 44: 206-209, 1997. Young, G., Resca, H. CT., and Sullivan, M. T.: The Yeasts of the Normal Mouth and Their Krlation to Salivary Acidity, J. Dent. Res. 30: 426-430, 1951. l~onesvoll I’., et al.: Retention of Chlorl~cxidine in the Hum:Ln Oral Cavity dftrr Mouth Kinsw, Abch. Oral Hiol. 19: 209-212, 1971. Kolla. CT.. Ltie. H.. and &hi&t. C. K.: Retention of Chlorhexidinr in the Human Oral Cayit>, ~rcli: braI kiol. 16: 1109-11 16, 1971. I)avies. Ii. M.. et al.: The Effect of Tonical Apnlicntion of Chlorhexidine on thr J%:rcterial Coltrni&tion df the Teeth and Gingiw, J. Prriodbt. Res. 5: 96-101, 1970. (‘hil~lrm,
i. x. 9. 10. I I. 12. 13. I-k.
h’eprint
,1.,
Acta
requests
to:
In-. Arigdor Sharon I)epartmmt of Oral and Ramham Medical Center Haifa, Israel
Masillo-Facial
Rurgcrg
DEPARTRIENT
OF
BIOLOGY, SCHOOL
RARIBAZRZ OF
ORAL
ASD
1\IEDICAI,
JIAXILLO-FACIAL CENTER
AND
SURGERY,
LABORATORY
DEI’ARThIE:NT
OF
OF
ORLiL
MICROBIOLO(~~,
3IEDICINE
Eighteen leukemic patients were examined for the presence the oral cavity. Fifteen patients were found to be Candida patients were put on a chlorhexidine mouth rinse regimen. was clearly fungicidal in vitro, no decrease in Candida titer mouth rinse. The ineffectiveness of the drug in viro might location of Candida organisms in the oral mucosa.
of Can&& albicnns in “cvlrriers.” Nine of the Although chlorllexidine was obtained with tllv hc due to the specific
C
uudida, nlbictx~s, usually a saprophy-te in the oral cavities of many healthy persons, sometimes causes various fungal infections. Oral candidiasis, usually initiated by local trauma, I-3 is being treated successfully. However, widespread infclctions of Candida in the gastrointestinal and respiratory systems present major therapeutic problems and often may bc fatal. They may occur as a corn plivation in patients irradiated for malignant lesions of the head and neck’ and in leukemic patients who receive irnmurlosul)Pressivc therapy.“, ” Since the prcs(:nw of C’n)ldidn crlbicw~s in the oral cavity appears to lx the starting point of infection, it is desirable to detect Candida “carriers” among these patients and to rctluce the danger of widespread infections by means of a specific prophylactic agcllt. Chlorhexidine is one of the therapeutic agents suggest,edfor oral candidiasis.+’ &sides its well-known activity against dental plaque in viva, it was shown to cure mouth thrush in seriously diseased children” and denture stomatitis in edentulous patients.8 The fungicidal effect of chlorhesidine in vitro has been recently demonstrated.” The purpose of the present stutlp was to determine the incidence of oral 201
MATERIALS
AND
METHODS
pcrimcntaI trch;ltnrcsllt with 0.2 l)(‘r cent c~hIorhexidinc~mouth rinses. The patients were instructetl to rinse for 1 minute>with 10 ml. of solution. They rind t~wicc daily for the first wwk, then st,oplwtl rinsing for 1 week, and started again four times per day for another week. Sali\-ary samples ww dlccttd 1 wek befow t,rcatmcnt and sew1~~1times tluring the c~sperimcnt. On the first, (lay it WEH COGIcctM just brfow, imnl~Xli;~tc~l~~ after, aiitl 30 minutes I’ollowing the first riirw. Saliva was the11wllwtotl onw :I ILcd~ for 4 wcel~s. 7%~ candida titer was ostahlishctl for ever,v sample. The cffcct of vhlorhcsidinv on (‘~r~did~ trlbicco~swas testetl in vitro. ~Ihlorhesicline glwoiiatc~ at different wncentrations was a~ltletl to a solution of Cnxdid0 trlhictr~rs (5 s 1W per milliliter). Samples of 0.1 ml. wrt taken at, l-minute illtcrrals for 3 niinulw and analyxctl as abo\-cx.
RESULTS
There was no clinical evitlww oi’ (‘andida in the oral cavity of the eighteen I)iiticlnts suffering from chronic. leukemia. II OWPLY~~, in fifteen of thcxpatients the salivary titers OF (‘alltlitlil i*aiig!.cylbct\\ecln 10” all(l 10’ ]x’r milliliter, ancl thPSc patients were clcfillcd as “( liHltlitl:l c~arricrs.“ ‘I%(~ (‘;llldicli~ tikrs of Iiinc I)i~ti(~lliS who i~inscvl \vith c~hlorht~siclinearc presentcd in Table J. No significant (Icc~rc:awill titctr was found in any of the paticnts. Al)art from a slight taste tiisordcr in son~e,thv patients did not complain of ari?’ sidt effects (luring the rilisiilg lwriod. The action ot‘ c~hlorhcsiclinc~OII (‘;tntlitli~ in vitro is demonstrated in Table II.
I. The titer of Candida in saliva during (microorganisms per milliliter)
Table
PaIiWll ?YO
I
3 5 4 5 6 7 h Y
Sample 0
I
2
/
chlorhexidine
rinses
No.
3
4
5
6
7
I X10’
I.1 x 10’
6.5 x IO5
4 3.3 I.5 2 1.5 5 3 I.5
37 2 3 5 5 1 I
32 8 5 5
x103 Xl02 x103 x103
41 xXl03IO”
45x xro210’
61.5 x10’ x IO’
3x 6X
1 XIOS 3x lo3
3 Go4 3x I03
2 X104 2x104
I Xl03 -
-
6 8
x102 Xl02
4 x102 4x 103
2x
2
5 x102 -
5x
Xl02 x IO’ x 103 Xl03 x IO’ x103 x103 x IO”
x10* X10’ Xl03 X10’ x103 x102 x103 x103
4
1
103
x103
x103
I x 103 I03 IO2
3 hl03
-
10”
Samples (time of collection) : 0 - One week before rinsing. I - Immediately before rinsing. 2 - 30 minutes following rinsing. :j - After one week of rinsing (x2). 1 - After one week without rinsing. .i After another week of rinsing (x4). pi - After another week without rinsing. 7 - After one rinse with placebo.
The in vitro effect of chlorhexidine per milliliter)
Table
C‘hlorhexidine concentration (ALglml. I 200 400 500 600 700 800
Table
on Catldida albicans
II.
Time 0 5x 5x 5x 5x 5x 5X
The influence
Ill.
of incubation
I lo7 IO7 IO7 IO7 IO7 107
I x 5x 6X 2x I x
IO8 105 IO3 102 10’
Time
of incubation
0
I
I
1 x 105
1 x 102
23
6x 5x
5x 1 x 10’ 102
10” lo6
(minures) 2
3
8X 10’ 5x IO’ 1 x IO” 0 i
I x IO’ 5x I03 I x IO’ 0 0 0
0
of saliva on the effectiveness
Sanlnle x;.
(microorganisms
of chlorhexidine (minutes) 2
3 0
22x x0103 102
:
Chlorhexidine gluconate in very low concentrations lowered the titer of Candida considerably. A solution of 600 pg/ml brought the fungal titer to zero within 2 minutes. At 800 pg/ml., 1 minute was enough to sterilize the solution. The influence of saliva on the effectiveness of chlorhexidine is demonstrated in Table III. Sterilization of all three samples was achieved within 3 minutes. It is evident that saliva did not inhibit the fungi&la1 effect of chlorhexidine. Table IV shows the change in titer of Candida following a single mouth rinse. Four “carriers” had an initial titer ranging between 2.5 x 102/ml. and 7.5 x
t I4hjcc.f I
0 4
Xl03
1
I
,
0
2.5 x 103
? 2x
i IO3
I 1
4 7x
IO3
.: 3
YIO”
udablished, It istherefore prold~lc thatCandida organisms arecontinuonsly rclcascclfrom the oral mucosa where they are not effectively exposedto the drug. Whereas chlorhcsidine is very effective against dental plaque because of its absorption to the tceth,‘“~ I4 it was practically ineffective in Candida “carriers.” Its moclr~ of action on the fungal cells will be sul)jectctl to further investigations. \Vr would like to thank the staff their 11~11) in selecting and examining :lnc’,l.
of the Hematology the patients and
Department Mrs. A. Hxrari
and Dr. 811. Grinman for for her technical assist-
REFERENCES 1. .Jcnkins, 2. 3. 4.
.i. 6.
nlbicms, ~Iasrlla, Hilastin Olsen Scani (‘hen, Cancer Mirsky, Igig. langslct,
IV. M. M., T~IO~RS, H. C., and Mason, 1). I<. : Oral Infections With Cantlidn Hrott. Med. J. 18: 192-200, 1973. H. P., Holan, Ch.T., and Laney, W. R.: The Prevention of Growth of Candida on 390 Soft Liner for I)entures, J. Prosthet. Dent. 33: 250-257, 1975. 1.: Denture Stomutitis: Occurrence and I)i.strilmtion of Fungi, Acta Odontol. 32: 329-331 1074 . . T. I’., and ‘<\‘el,ster, J. 11.: Oral Monilia Study on Patients With Head and Neck DuringRadiotherapy, Cancer 34: 246-249, 197< H. R., and Cuttner, J. : Fungal Infection in ;\cute Leukemia, Cancer 30: 348-352,
et al. : Cl~lorhesidinc~ Treatment of Oral Canclidiasis in 8criously Diseased Pardiatr. Sand. 63: X09-81 1, 1971. J. Clin. Periodont,ol. 1: 1X1-152, 1974. C~j~rmo, P. : Chlorlrrsidinc~ in J)rntal Practice, J~udt~-.Jiirgc,nsnl, E., and Liie, If. : Cklorhesidine as :I Hrnture Disinfectant in the Treatment of I)rnture Rtomatitis, Stand. .J. Hcwt. Res. 80: 137-464, 1972. I?crtlicevsky, l., et al. : Tlic Effect of (:hlorhexidine on ~‘crndidn crlbitnns In Vitro. (In prcparation.) Rerdiwvsky, J., et al. : d Strip ‘lost for Hetectirrg Candida in tile Oral Cal-ity, O~.\I) StTt:o. 44: 206-209, 1997. Young, G., Resca, H. CT., and Sullivan, M. T.: The Yeasts of the Normal Mouth and Their Krlation to Salivary Acidity, J. Dent. Res. 30: 426-430, 1951. l~onesvoll I’., et al.: Retention of Chlorl~cxidine in the Hum:Ln Oral Cavity dftrr Mouth Kinsw, Abch. Oral Hiol. 19: 209-212, 1971. Kolla. CT.. Ltie. H.. and &hi&t. C. K.: Retention of Chlorhexidinr in the Human Oral Cayit>, ~rcli: braI kiol. 16: 1109-11 16, 1971. I)avies. Ii. M.. et al.: The Effect of Tonical Apnlicntion of Chlorhexidine on thr J%:rcterial Coltrni&tion df the Teeth and Gingiw, J. Prriodbt. Res. 5: 96-101, 1970. (‘hil~lrm,
i. x. 9. 10. I I. 12. 13. I-k.
h’eprint
,1.,
Acta
requests
to:
In-. Arigdor Sharon I)epartmmt of Oral and Ramham Medical Center Haifa, Israel
Masillo-Facial
Rurgcrg