ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Mar. 1975, Copyright © 1975 American Society for Microbiology
p.
294-297
Vol. 7, No. 3 Printed in U.S.A.
Effect of Rifampin on Nasal Carriage of Staphylococcus aureus MERLE A. SANDE* AND GERALD L. MANDELL Division of Infectious Diseases, Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22903 Received for publication 24 October 1974
Initial studies indicate that rifampin may be useful for the treatment of Staphylococcus aureus infections. Because bacterial resistance to rifampin may develop rapidly, its widespread use could result in the emergence of a resistant flora. This study evaluates the effectiveness of rifampin in reducing the nasal carriage of S. aureus and the rate at which resistant mutants emerge in a tuberculosis hospital where the drug was widely used. Anterior nares cultures were performed four times over a 13-month period. Carriage rates of S. aureus were 1.7% in 227 patients receiving rifampin, 7 .8% in 190 patients receiving other antituberculous therapy, and 14.2% in 98 hospital employees (rifampin-treated versus other patients. P < 0.003; rifampin-treated versus employees, P < 0.001; employees versus other patients, P = 0.157). All four strains of S. aureus isolated from patients on rifampin therapy were rifampin resistant. All 16 strains isolated from patients not on rifampin and 15 of 16 strains isolated from hospital personnel were susceptible. One instance of apparent spread of a rifampin-resistant organism occurred in a hospital attendant who had never received rifampin.
Rifampin is a valuable antibiotic for the therapy of tuberculosis and is effective in eradicating the meningococcal carrier state (4, 15). Rifampin has several unique characteristics which may also make it useful in the therapy of staphylococcal infections. Most strains are exquisitely susceptible to low concentrations of the drug; the minimal inhibitory concentration (MIC) was less than 0.04 gg/ml for 98% of clinically isolated strains reported from Switzerland (16). These levels are greatly exceeded in the serum with the 600-mg daily dose recommended for the therapy of tuberculosis (range, 7 to 9 ,g/ml at 2 h and 0.2 ug/ml at 24 h) (14). The drug penetrates into nasal pharyngeal secretions (tears and saliva) in relatively high concentrations (1 to 2 ,ug/ml), a property that may make rifampin useful in eradicating the staphylococcal nasal carrier state (5). Also, rifampin has been shown to enter phagocytes and kill intracellular bacteria, a location where living bacteria are protected from many other antibiotics (10, 11). This unique characteristic may explain the drug's ability to sterilize staphylococcal abscesses in experimental animals more effectively than other antibiotics (8). Rifampin has been used in limited clinical trials in Europe for infections caused by Staphylococcus aureus.. However, when rifampin was used alone, resistant strains have emerged rapidly during therapy (3). The same phenomenon has been observed in experimental staphylococcal endocarditis treated with rifampin (12). 294
In vitro, highly resistant organisms emerged spontaneously with a mutation rate of 2 x 10-8 bacteria per division cycle and exist naturally with a frequency of 10-7 colony-forming units (3, 7). Rifampin resistance occurs as a one-step mutation (strains susceptible to less than 0.04 ,gg/ml become resistant to more than 512 gg/ml in one generation) as a result of the development of ribonucleic acid polymerase, which will not bind rifampin. Therefore, one might predict that resistant organisms will emerge during single drug therapy with rifampin for any infection in which large numbers of staphylococci are present. McCabe and Lorian predicted that a majority of strains of staphylococci indigenous to hospitals would rapidly become resistant to rifampin within a few months after its introduction into hospital practice (9). The purpose of this study was to investigate the impact of rifampin on the nasal carriage of S. aureus in a tuberculosis hospital where the drug was widely used. This was done by determining the rate of staphylococcal nasal carriage, the incidence of isolates resistant to rifampin, and the spread of these resistant strains. MATERIALS AND METHODS Five hundred and eighty-four nasal cultures were taken on 515 different adult inpatients and hospital personnel at the Blue Ridge Sanatorium in Charlottesville, Va. These were divided into three groups: (i) 227 were adult patients receiving rifampin along with
295
RIFAMPIN AND STAPHYLOCOCCI CARRIAGE
VOL. 7, 1975
other antituberculous drugs (patients receiving other drugs with antistaphylococcal activity such as streptomycin were excluded); (ii) 190 were adult patients receiving antituberculous drugs other than rifampin; and (iii) 98 were hospital employees. Cultures were collected on four different occasions over a 13-month period. Most subjects were cultured only once; however, 17 of the 227 patients in group (i) were cultured twice and two were cultured three times. Fourteen of the 190 patients in group (ii) were cultured twice. Nineteen of the 98 hospital personnel [group (iii)] were cultured twice, and nine were cultured on three occasions. Several patients were followed after discharge and recultured by local public health officials. Saline (without preservative) was used to moisten small calganite swabs (Wilson Diagnostics, Inc., Glenwood, Ill.), which were vigorously twisted in the anterior nares and immediately streaked on 5% sheep blood agar plates. After incubation for 24 h at 37 C, suspicious colonies were tested for coagulase, deoxyribonuclease, and mannitol fermentation. Organisms that satisfied these criteria were identified as S. aureus and included in the study. All isolates were screened for rifampin resistance by streaking on nutrient agar plates which contained 1.0 and 10 gg of rifampin per ml. Serial tube dilutions were performed on all strains resistant to 10 vg of rifampin per ml in order to quantitate the degree of resistance. Phage typing was done on 33 of the S. aureus isolates by Edward Konopka, Ciba Laboratories, using 23 phages (6). Antibiograms of the non-phagetypable S. aureus strains were obtained using the Kirby-Bauer disk sensitivity method and 11 antibiotics (1).
RESULTS Nasal carrier rates of S. aureus were significantly lower in patients receiving rifampin (1.7%) than in either tuberculosis patients receiving other forms of therapy (7.9'7c, P < 0.003 by chi-square analysis) or hospital employees not receiving any antimicrobial therapy (14.2%, P < 0.001) (Table 1). All 15 patients not receiving rifampin, and 13 of 14 hospital employees who were found to be nasal carriers, had rifampin-susceptible strains of S. aureus
(MIC < 0.015 ,g/ml). A single hospital attendnever received the drug, carried a rifampin-resistant nontypable Staphylococcus on one occasion; however, when cultured 4 months later, S. aureus was not isolated. The four patients found to be S. aureus nasal carriers in the rifampin-treated group all harbored highly resistant strains (MIC > 512 ,ug/ml). One patient carrying a rifampin-resistant nontypable S. aureus died of unrelated causes, and another with a nontypable Staphylococcus was lost to follow-up. The other two patients continued to carry S. aureus for at least 1 year after the time of initial isolation. One was discharged but has remained on rifampin therapy. She has been cultured on four different occasions and each time S. aureus phage type 52A/79 (group [i] resistant to rifampin (MIC > 512 ,ug/ml) was isolated. Ritampin was discontinued in the other carrier, but he continued to carry the rifampin-resistant S. aureus of the same phage type (53/75/83A) 4 months later. A subsequent culture taken at 10 months again revealed S. aureus; however, the phage type had changed (nontypable) and it was now susceptible to rifampin (MIC < 0.015). There was no increase in the number of rifampin-resistant S. aureus isolated from the study population over the 13-month studv period. These strains were not found in roommates or other patients not on rifampin. In only one instance did a hospital attendant become a transient carrier of rifampin-resistant S. aureus. A predominant phage type was not present in this population. Two group (I} (52A/79), a single group (II) (3C/55/61), and six group (III) (53/83A, 83A, 42E/77/83A, 47/53/54/75/77/83A/ 84/85, 6/42E/47/53/54/75/83A, and 6/47/53/ 54/75/83A/85) were found. Fifteen strains were untypable by the 23-phage panel employed, and antibiograms were performed with 11 antibiotics. Five strains had a common pattern (resistant to penicillin and ampicillin and susceptible to all other antibiotics tested), three strains ant, who had
TABLE 1. Nasal carriage of S. aureus Individual patients not on rifampin
Individual patients on rifampin Date Date
~~~~No.of No.apositive cultured |. aureus
April 1972 July 1972 November 1972 May 1973 a
52 49 55 71
1 0 3 0
1 0 3 0
Employees
~~~No. No. of
No.
rifamSaues to pina
E
N cultured
Spositive
resistant
No. cultured
41 45 68 36
3 5 3 4
0 0 0
27 33 27 11
.aru
to rifampin
0
S. aureus was not inhibited by greater than 512 jig of rifampin per ml.
X.o positive
No. resistant
3 3 6 2
0 0 0 1
S. aureus to rifampin
296
SANDE AND MANDELL
were susceptible to all 11 antibiotics, three strains were susceptible to eight antibiotics, and the remaining four strains all had different patterns of antibiotic resistance. The rifampin-resistant isolates included one group (I) one group (III), and three nontypable strains with three different antibiograms. Others have shown that rifampin-resistant staphylococcal mutants retain the same phage type as the parent organism (9).
DISCUSSION This study has demonstrated that patients receiving rifampin have a reduced incidence of S. aureus in their anterior nares when compared with patients receiving other antituberculous therapy or with hospital personnel. This might be explained by the excellent penetration of the drug into nasal secretions and the initial susceptibility of nearly all strains of S. aureus to the antimicrobial agent (5, 16). Organisms highly resistant to rifampin emerged, as one might have predicted, in some of those patients receiving the drug alone. If the assumption is made that the carriage rate of all patients was initially the same, the data suggests that 20% of those treated with rifampin alone developed resistant staphylococcal strains, whereas S. aureus was eliminated from the other 80% and further acquisition was prevented. The behavior of the resistant strains in the two cases of staphylococcal carriage followed for 10 and 14 months suggested that constant rifampin therapy may be important for persistence of the resistant mutants. The duration of nasal carriage of the rifampin-susceptible S. aureus in groups (II) and (III) was variable. The organism was isolated from six of the 33 subjects who were cultured on more than one occasion. Two were positive on consecutive periods, whereas two acquired and two lost the organism during the study period. Thus far rifampin-resistant strains of S. aureus have not emerged as predominant organisms in the tuberculosis hospital, even though rifampin has been used extensively for 3 years. Likewise, we have been unable to detect any patient-to-patient spread, although transient colonization of an attendant by a rifampinresistant strain of S. aureus did occur on one occasion.
It should be noted that this study was done in chronic care facility used for tuberculosis patients and the rate of staphylococcal carriage was lower than that reported in other hospital patients (13). Emergence of resistance and person-to-person spread might have been higher if a
ANTIMICROB. AGENTS CHEMOTHER.
rifampin had been used alone in an acute hospital with open wounds, staphylococcal abscesses, and a higher rate of nasal carriage. However, failure of rifampin-resistant meningococcal strains to spread rapidly and dominate the sensitive flora has also been observed after mass therapy with rifampin in a closed population (2). Results of this study suggest: (i) rifampin may be effective in eliminating the nasal carriage of S. aureus; (ii) when rifampin is used as a single antistaphylococcal agent, resistant strains will emerge; (iii) all rifampin-resistant organisms are separable- by either phage typing or antibiograms into distinct strains; and (iv) rifampin-resistant strains of S. aureus show minimal spread, as indicated by the fact that in an area where the drug was intensively used the staphylococcal flora remained predominantly susceptible. ACKNOWLEDGMENTS We thank Forrest W. Pitts, Medical Director of the Blue Ridge Sanatorium, and Martha Coleman for their helpful assistance, Joy W. Skaar and Kip B. Courtney for expert technical assistance, and Cathy L. Beach for secretarial assistance. This study was supported by a grant from the CIBA-Geigy Corporation. Dr. Mandell is the holder of Public Health Service research career development award GM-49504 from the National Institute of General Medical Sciences. LITERATURE CITED 1. Bauer, A. W., W. M. Kirby, J. C. Sherris, and M. Turck. 1966. Antibiotic susceptibility testing by a standardized single disk method. Am. J. Clin. Pathol. 45:493-469. 2. Beam, W. E., Jr., N. R. Newberg, L. F. Devine, W. E. Pierce, and J. A. Davies. 1971. The effect of rifampin on the nasopharyngeal carriage of Neisseria meningitidis in a military population. J. Infect. Dis. 124:39-46. 3. Binda, G., E. Domenichini, A. Gottardi, et al. 1971. Rifampin, a general review. Arzneim.-Forsch. 21:1908-1977. 4. Deal, W. B., and E. Sanders. 1969. Efficacy of rifampin in treatment of meningococcal carriers. New Engl. J. Med. 281:641-645. 5. Hoeprich, P. D. 1971. Prediction of antimeningococcic chemoprophylactic efficacy. J. Infect. Dis. 123:125-133. 6. Jackson, G. G., H. F. Dowling, and M. H. Lepper. 1954. Bacteriophage typing of staphylococci. I. Techniques and pattern of lysis. J. Lab. Clin. Mgd. 44:14-28. 7. Kunin, C. M., D. Broudt, and H. Wood. 1969. Bacteriologic studies of rifampin, a new semi-synthetic antibiotic. J. Infect. Dis. 119:132-137. 8. Lobo, M. C., and G. L. Mandell. 1972. Treatment of experimental staphylococcal infection with rifampin. Antimicrob. Agents Chemother. 2:195-200. 9. McCabe, W. R., and V. Lorian. 1968. Comparison of the antibacterial activity of rifampicin and other antibiotics. Am. J. Med. Sci. 256:255-265. 10. Mandell, G. L. 1973. The interaction of intraleukocytic bacteria and antibiotics. J. Clin. Invest. 52:1673-1679. 11. Mandell, G. L., and T. K. Vest. 1972. Killing of intraleukocytic Staphylococcus aureus by rifampin: in
VOL. 7, 1975
RIFAMPIN AND STAPHYLOCOCCI CARRIAGE
vitro and in vivo studies. J. Infect. Dis. 125:486-490. 12. Sande, M. A., and M. L. Johnson. 1973. Antibiotic therapy in experimental staphylococcal endocarditis. J. Clin. Invest. 52:72a-73a. 13. Solberg, C. 0. 1965. A study of carriers of Staphylococcus aureus. Acta Med. Scand. 178(Suppl. 436):1-96. 14. Verbist, L., and A. Gyselen. 1968. Antituberculous activity of rifampin in vitro and in vivo and the concentrations attained in human blood. Am. Rev. Respir. Dis.
297
98:923-932. 15. Weinstein, L. 1970. Drugs used in the chemotherapy of leprosy and tuberculosis, p. 1333-1334. In L. S. Goodman and A. Gilman (ed.), The pharmacological basis of therapeutics. The MacMillan Co., New York. 16. Zak, C., J. Hawiger, and J. Jeljaszwicz. 1969. Sensitivity of Staphylococcus aureus to 30 antibiotics. Chemotherapy (Basel) 14:7-22.
p.
294-297
Vol. 7, No. 3 Printed in U.S.A.
Effect of Rifampin on Nasal Carriage of Staphylococcus aureus MERLE A. SANDE* AND GERALD L. MANDELL Division of Infectious Diseases, Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22903 Received for publication 24 October 1974
Initial studies indicate that rifampin may be useful for the treatment of Staphylococcus aureus infections. Because bacterial resistance to rifampin may develop rapidly, its widespread use could result in the emergence of a resistant flora. This study evaluates the effectiveness of rifampin in reducing the nasal carriage of S. aureus and the rate at which resistant mutants emerge in a tuberculosis hospital where the drug was widely used. Anterior nares cultures were performed four times over a 13-month period. Carriage rates of S. aureus were 1.7% in 227 patients receiving rifampin, 7 .8% in 190 patients receiving other antituberculous therapy, and 14.2% in 98 hospital employees (rifampin-treated versus other patients. P < 0.003; rifampin-treated versus employees, P < 0.001; employees versus other patients, P = 0.157). All four strains of S. aureus isolated from patients on rifampin therapy were rifampin resistant. All 16 strains isolated from patients not on rifampin and 15 of 16 strains isolated from hospital personnel were susceptible. One instance of apparent spread of a rifampin-resistant organism occurred in a hospital attendant who had never received rifampin.
Rifampin is a valuable antibiotic for the therapy of tuberculosis and is effective in eradicating the meningococcal carrier state (4, 15). Rifampin has several unique characteristics which may also make it useful in the therapy of staphylococcal infections. Most strains are exquisitely susceptible to low concentrations of the drug; the minimal inhibitory concentration (MIC) was less than 0.04 gg/ml for 98% of clinically isolated strains reported from Switzerland (16). These levels are greatly exceeded in the serum with the 600-mg daily dose recommended for the therapy of tuberculosis (range, 7 to 9 ,g/ml at 2 h and 0.2 ug/ml at 24 h) (14). The drug penetrates into nasal pharyngeal secretions (tears and saliva) in relatively high concentrations (1 to 2 ,ug/ml), a property that may make rifampin useful in eradicating the staphylococcal nasal carrier state (5). Also, rifampin has been shown to enter phagocytes and kill intracellular bacteria, a location where living bacteria are protected from many other antibiotics (10, 11). This unique characteristic may explain the drug's ability to sterilize staphylococcal abscesses in experimental animals more effectively than other antibiotics (8). Rifampin has been used in limited clinical trials in Europe for infections caused by Staphylococcus aureus.. However, when rifampin was used alone, resistant strains have emerged rapidly during therapy (3). The same phenomenon has been observed in experimental staphylococcal endocarditis treated with rifampin (12). 294
In vitro, highly resistant organisms emerged spontaneously with a mutation rate of 2 x 10-8 bacteria per division cycle and exist naturally with a frequency of 10-7 colony-forming units (3, 7). Rifampin resistance occurs as a one-step mutation (strains susceptible to less than 0.04 ,gg/ml become resistant to more than 512 gg/ml in one generation) as a result of the development of ribonucleic acid polymerase, which will not bind rifampin. Therefore, one might predict that resistant organisms will emerge during single drug therapy with rifampin for any infection in which large numbers of staphylococci are present. McCabe and Lorian predicted that a majority of strains of staphylococci indigenous to hospitals would rapidly become resistant to rifampin within a few months after its introduction into hospital practice (9). The purpose of this study was to investigate the impact of rifampin on the nasal carriage of S. aureus in a tuberculosis hospital where the drug was widely used. This was done by determining the rate of staphylococcal nasal carriage, the incidence of isolates resistant to rifampin, and the spread of these resistant strains. MATERIALS AND METHODS Five hundred and eighty-four nasal cultures were taken on 515 different adult inpatients and hospital personnel at the Blue Ridge Sanatorium in Charlottesville, Va. These were divided into three groups: (i) 227 were adult patients receiving rifampin along with
295
RIFAMPIN AND STAPHYLOCOCCI CARRIAGE
VOL. 7, 1975
other antituberculous drugs (patients receiving other drugs with antistaphylococcal activity such as streptomycin were excluded); (ii) 190 were adult patients receiving antituberculous drugs other than rifampin; and (iii) 98 were hospital employees. Cultures were collected on four different occasions over a 13-month period. Most subjects were cultured only once; however, 17 of the 227 patients in group (i) were cultured twice and two were cultured three times. Fourteen of the 190 patients in group (ii) were cultured twice. Nineteen of the 98 hospital personnel [group (iii)] were cultured twice, and nine were cultured on three occasions. Several patients were followed after discharge and recultured by local public health officials. Saline (without preservative) was used to moisten small calganite swabs (Wilson Diagnostics, Inc., Glenwood, Ill.), which were vigorously twisted in the anterior nares and immediately streaked on 5% sheep blood agar plates. After incubation for 24 h at 37 C, suspicious colonies were tested for coagulase, deoxyribonuclease, and mannitol fermentation. Organisms that satisfied these criteria were identified as S. aureus and included in the study. All isolates were screened for rifampin resistance by streaking on nutrient agar plates which contained 1.0 and 10 gg of rifampin per ml. Serial tube dilutions were performed on all strains resistant to 10 vg of rifampin per ml in order to quantitate the degree of resistance. Phage typing was done on 33 of the S. aureus isolates by Edward Konopka, Ciba Laboratories, using 23 phages (6). Antibiograms of the non-phagetypable S. aureus strains were obtained using the Kirby-Bauer disk sensitivity method and 11 antibiotics (1).
RESULTS Nasal carrier rates of S. aureus were significantly lower in patients receiving rifampin (1.7%) than in either tuberculosis patients receiving other forms of therapy (7.9'7c, P < 0.003 by chi-square analysis) or hospital employees not receiving any antimicrobial therapy (14.2%, P < 0.001) (Table 1). All 15 patients not receiving rifampin, and 13 of 14 hospital employees who were found to be nasal carriers, had rifampin-susceptible strains of S. aureus
(MIC < 0.015 ,g/ml). A single hospital attendnever received the drug, carried a rifampin-resistant nontypable Staphylococcus on one occasion; however, when cultured 4 months later, S. aureus was not isolated. The four patients found to be S. aureus nasal carriers in the rifampin-treated group all harbored highly resistant strains (MIC > 512 ,ug/ml). One patient carrying a rifampin-resistant nontypable S. aureus died of unrelated causes, and another with a nontypable Staphylococcus was lost to follow-up. The other two patients continued to carry S. aureus for at least 1 year after the time of initial isolation. One was discharged but has remained on rifampin therapy. She has been cultured on four different occasions and each time S. aureus phage type 52A/79 (group [i] resistant to rifampin (MIC > 512 ,ug/ml) was isolated. Ritampin was discontinued in the other carrier, but he continued to carry the rifampin-resistant S. aureus of the same phage type (53/75/83A) 4 months later. A subsequent culture taken at 10 months again revealed S. aureus; however, the phage type had changed (nontypable) and it was now susceptible to rifampin (MIC < 0.015). There was no increase in the number of rifampin-resistant S. aureus isolated from the study population over the 13-month studv period. These strains were not found in roommates or other patients not on rifampin. In only one instance did a hospital attendant become a transient carrier of rifampin-resistant S. aureus. A predominant phage type was not present in this population. Two group (I} (52A/79), a single group (II) (3C/55/61), and six group (III) (53/83A, 83A, 42E/77/83A, 47/53/54/75/77/83A/ 84/85, 6/42E/47/53/54/75/83A, and 6/47/53/ 54/75/83A/85) were found. Fifteen strains were untypable by the 23-phage panel employed, and antibiograms were performed with 11 antibiotics. Five strains had a common pattern (resistant to penicillin and ampicillin and susceptible to all other antibiotics tested), three strains ant, who had
TABLE 1. Nasal carriage of S. aureus Individual patients not on rifampin
Individual patients on rifampin Date Date
~~~~No.of No.apositive cultured |. aureus
April 1972 July 1972 November 1972 May 1973 a
52 49 55 71
1 0 3 0
1 0 3 0
Employees
~~~No. No. of
No.
rifamSaues to pina
E
N cultured
Spositive
resistant
No. cultured
41 45 68 36
3 5 3 4
0 0 0
27 33 27 11
.aru
to rifampin
0
S. aureus was not inhibited by greater than 512 jig of rifampin per ml.
X.o positive
No. resistant
3 3 6 2
0 0 0 1
S. aureus to rifampin
296
SANDE AND MANDELL
were susceptible to all 11 antibiotics, three strains were susceptible to eight antibiotics, and the remaining four strains all had different patterns of antibiotic resistance. The rifampin-resistant isolates included one group (I) one group (III), and three nontypable strains with three different antibiograms. Others have shown that rifampin-resistant staphylococcal mutants retain the same phage type as the parent organism (9).
DISCUSSION This study has demonstrated that patients receiving rifampin have a reduced incidence of S. aureus in their anterior nares when compared with patients receiving other antituberculous therapy or with hospital personnel. This might be explained by the excellent penetration of the drug into nasal secretions and the initial susceptibility of nearly all strains of S. aureus to the antimicrobial agent (5, 16). Organisms highly resistant to rifampin emerged, as one might have predicted, in some of those patients receiving the drug alone. If the assumption is made that the carriage rate of all patients was initially the same, the data suggests that 20% of those treated with rifampin alone developed resistant staphylococcal strains, whereas S. aureus was eliminated from the other 80% and further acquisition was prevented. The behavior of the resistant strains in the two cases of staphylococcal carriage followed for 10 and 14 months suggested that constant rifampin therapy may be important for persistence of the resistant mutants. The duration of nasal carriage of the rifampin-susceptible S. aureus in groups (II) and (III) was variable. The organism was isolated from six of the 33 subjects who were cultured on more than one occasion. Two were positive on consecutive periods, whereas two acquired and two lost the organism during the study period. Thus far rifampin-resistant strains of S. aureus have not emerged as predominant organisms in the tuberculosis hospital, even though rifampin has been used extensively for 3 years. Likewise, we have been unable to detect any patient-to-patient spread, although transient colonization of an attendant by a rifampinresistant strain of S. aureus did occur on one occasion.
It should be noted that this study was done in chronic care facility used for tuberculosis patients and the rate of staphylococcal carriage was lower than that reported in other hospital patients (13). Emergence of resistance and person-to-person spread might have been higher if a
ANTIMICROB. AGENTS CHEMOTHER.
rifampin had been used alone in an acute hospital with open wounds, staphylococcal abscesses, and a higher rate of nasal carriage. However, failure of rifampin-resistant meningococcal strains to spread rapidly and dominate the sensitive flora has also been observed after mass therapy with rifampin in a closed population (2). Results of this study suggest: (i) rifampin may be effective in eliminating the nasal carriage of S. aureus; (ii) when rifampin is used as a single antistaphylococcal agent, resistant strains will emerge; (iii) all rifampin-resistant organisms are separable- by either phage typing or antibiograms into distinct strains; and (iv) rifampin-resistant strains of S. aureus show minimal spread, as indicated by the fact that in an area where the drug was intensively used the staphylococcal flora remained predominantly susceptible. ACKNOWLEDGMENTS We thank Forrest W. Pitts, Medical Director of the Blue Ridge Sanatorium, and Martha Coleman for their helpful assistance, Joy W. Skaar and Kip B. Courtney for expert technical assistance, and Cathy L. Beach for secretarial assistance. This study was supported by a grant from the CIBA-Geigy Corporation. Dr. Mandell is the holder of Public Health Service research career development award GM-49504 from the National Institute of General Medical Sciences. LITERATURE CITED 1. Bauer, A. W., W. M. Kirby, J. C. Sherris, and M. Turck. 1966. Antibiotic susceptibility testing by a standardized single disk method. Am. J. Clin. Pathol. 45:493-469. 2. Beam, W. E., Jr., N. R. Newberg, L. F. Devine, W. E. Pierce, and J. A. Davies. 1971. The effect of rifampin on the nasopharyngeal carriage of Neisseria meningitidis in a military population. J. Infect. Dis. 124:39-46. 3. Binda, G., E. Domenichini, A. Gottardi, et al. 1971. Rifampin, a general review. Arzneim.-Forsch. 21:1908-1977. 4. Deal, W. B., and E. Sanders. 1969. Efficacy of rifampin in treatment of meningococcal carriers. New Engl. J. Med. 281:641-645. 5. Hoeprich, P. D. 1971. Prediction of antimeningococcic chemoprophylactic efficacy. J. Infect. Dis. 123:125-133. 6. Jackson, G. G., H. F. Dowling, and M. H. Lepper. 1954. Bacteriophage typing of staphylococci. I. Techniques and pattern of lysis. J. Lab. Clin. Mgd. 44:14-28. 7. Kunin, C. M., D. Broudt, and H. Wood. 1969. Bacteriologic studies of rifampin, a new semi-synthetic antibiotic. J. Infect. Dis. 119:132-137. 8. Lobo, M. C., and G. L. Mandell. 1972. Treatment of experimental staphylococcal infection with rifampin. Antimicrob. Agents Chemother. 2:195-200. 9. McCabe, W. R., and V. Lorian. 1968. Comparison of the antibacterial activity of rifampicin and other antibiotics. Am. J. Med. Sci. 256:255-265. 10. Mandell, G. L. 1973. The interaction of intraleukocytic bacteria and antibiotics. J. Clin. Invest. 52:1673-1679. 11. Mandell, G. L., and T. K. Vest. 1972. Killing of intraleukocytic Staphylococcus aureus by rifampin: in
VOL. 7, 1975
RIFAMPIN AND STAPHYLOCOCCI CARRIAGE
vitro and in vivo studies. J. Infect. Dis. 125:486-490. 12. Sande, M. A., and M. L. Johnson. 1973. Antibiotic therapy in experimental staphylococcal endocarditis. J. Clin. Invest. 52:72a-73a. 13. Solberg, C. 0. 1965. A study of carriers of Staphylococcus aureus. Acta Med. Scand. 178(Suppl. 436):1-96. 14. Verbist, L., and A. Gyselen. 1968. Antituberculous activity of rifampin in vitro and in vivo and the concentrations attained in human blood. Am. Rev. Respir. Dis.
297
98:923-932. 15. Weinstein, L. 1970. Drugs used in the chemotherapy of leprosy and tuberculosis, p. 1333-1334. In L. S. Goodman and A. Gilman (ed.), The pharmacological basis of therapeutics. The MacMillan Co., New York. 16. Zak, C., J. Hawiger, and J. Jeljaszwicz. 1969. Sensitivity of Staphylococcus aureus to 30 antibiotics. Chemotherapy (Basel) 14:7-22.
![[A study of nasal carriage of methicillin-resistant Staphylococcus aureus].](/assets/img/hold.png)
