ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, June 1977, p. 1071-1073 Copyright 0 1977 American Society for Microbiology
Vol. 11, No. 6 Printed in U.S.A.
In Vitro Antibiotic Susceptibility of Salmonellae FACELUCIA BARROS, OKSANA M. KORZENIOWSKI, MERLE A. SANDE,* KATIA MARTINS, LUIZ CARLOS SANTOS, AND HEONIR ROCHA Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22901,* Department of Medicine, Federal University ofBahia, Salvador, Bahia, Brazil, and Couto Maia Hospital, Salvador, Bahia, Brazil. Received for publication 27 January 1977
In vitro antibiotic susceptibilities were determined for 101 strains of salmonellae. Resistance to chloramphenicol and ampicillin was low. Cefamandole was active against the majority of strains and deserves further evaluation.
The recent identification of chloramphenicol BLP-1761 (an ester of hetacillin, Bristol Laboand multiple drug-resistant salmonella epi- ratories, Syracuse, N.Y.). An inoculum of 104 demics has generated increased interest in the organisms was added to each tube. After 24 h of overall drug sensitivities of these organisms in incubation, samples were taken from all tubes various localities as well as a search for alter- with no visible growth and were plated on nate drug therapy when such resistant strains Trypticase soy agar to determine minimum are identified (4, 5). Cefamandole, a new paren- bactericidal concentrations. Strains of S. typhi teral cephalosporin prepared by substitution of (Fig. 1) were, in general, more susceptible to heterocyclic groups on 7-aminocephalosporanic the antimicrobial agents tested than the "nonacid, has been shown to have a marked effect on typhi" strains (Fig. 2). Cefamandole was the a small number of strains of Salmonella typhi most active drug by weight, with 100% of S. in vitro. To evaluate the potential usefulness of typhi strains inhibited by 1.56 gg/ml or less this antibiotic, 101 strains of salmonella, iso- (Fig. la). This is in contrast to other cephalolated in Salvador, Brazil, were tested in vitro to sporins previously tested (1, 2). Ninety-seven a variety of antibiotics currently in use or un- percent of S. typhi strains was inhibited by BLP-1761 at a concentration of 3.1 g.g/ml as der investigation. Strains studied. The 101 strains of salmo- opposed to 90% for ampicillin. Carbenicillin nella used in our evaluations were isolated was the least active of the penicillin derivafrom patients at the Hospital Professor Edgard tives. Chloramphenicol inhibited 97% of S. typhi Santos and the Hospital Couto Maia from 1972 to 1975. Both hospitals are referral centers for strains with concentrations of less than 12.5 patients with suspected or proven typhoid fever gg/ml (Fig. lb). Ninety-three percent of the and other infectious diseases. The salmonella strains was inhibited by 12.5 gg of tetracycline strains were collected randomly in an area per ml. Gentamicin and tobramycin had simiwhere typhoid fever is endemic, and no epi- lar activity with 93% of strains inhibited by a demic outbreak was documented during the concentration of less than 12.5 ,ug/ml. In contrast to S. typhi, the "non-typhi" salperiod of collection. Serotyping was performed on isolation and reconfirmed prior to antibiotic monella strains exhibited in vitro resistance of susceptibility testing. Of 59 strains of group D 30 to 40% to most antibiotics tested. CefamanS. typhi, 53 were recovered from blood, 4 from dole and BLP-1761 again appeared to be quite stools, and 2 from cerebralspinal fluid. Of the active, each inhibiting 70% of strains with conremaining 42 "non-typhi" salmonella strains, centrations of 1.6 ,ug/ml (Fig. 2a). 22 were recovered from blood, and 20 were isoIn this evaluation of 101 strains of salmolated from stool, cerebralspinal fluid, urine, or nella, only a minor emergence of resistant strains to the antibiotics currently utilized in synovial fluid. Antimicrobial testing. The minimum inhibi- the community was noted. High-level resisttory concentration for each drug was deter- ance to chloramphenicol and ampicillin remined by serial twofold dilutions in Trypticase mains in the 2 to 3% range, comparable to the soy broth with freshly prepared solutions of data of Finland et al. (2), but much less than chloramphenicol, ampicillin, carbenicillin, tet- the 16 to 33% range reported in other areas not racycline, tobramycin, gentamicin, cefaman- involved in an epidemic of chloramphenicoldole (Eli Lilly and Co., Indianapolis, Ind.), and resistant strains. 1071
1072
NOTES
ANTIMICROB. AGENTS CHEMOTHER. SALMONELLA TYPHI 100
-- - - - - -- -- ----
/!
so la
I
60
I
I
-C C
!
II
._
0
20
40
'
j
-AMPICKLLN ~~~CARBENICUllN zBPP-1761 20
20 " ! 1 l !
be
/1
-
GENTAMICIN
- -
TETRACYCLINE TOSRAMYCIN
.......
-- CEFAMAND)OLE
- -
CHLORAMPHENICOL
/ 0.19
035
3.
12.5
50
200
0.19
0.75
3.1
12.5
50
200
Concentration of Antibiotic
(Pg/ml) FIG. 1. (a) and (b) show antibiotic susceptibilities of 59 strains of S. typhi.
SALMONELLA NON-TYPHI /
1008
so
I
60 c~~~~~ -
I
1.
i/~ ~
-HOAPEIO
y
-CFMNOE ~~
IL
I HO A PEIO
CEAM ND LEI
0.19
075
3.1
12.5
50
200
Concentration of Antibiotic
(Mg/ml) FIG. 2. (a) and (b) show antibiotic susceptibilities of 42 strains of 'non-typhi" salmonellae.
NOTES
VOL. 11, 1977
Of note is the emergence of aminoglycoside resistance (7%), which has not been seen by other investigators (1-3). This decreased susceptibility to aminoglycosides is also found in the group of "non-typhi" strains, which showed up to 30% resistance to the maximum achievable serum levels. LITERATURE CITED 1. Bissett, M. L., S. L. Abbott, and R. M. Wood. 1974. Antimicrobial resistance and R factors in Salmonella isolated in California (1971-1972). Antimicrob.
Agents Chemother. 5:161-168.
1073
2. Finland, M., C. Garmer, C. Wilcox, and L. Sabath. 1974. Salmonellosis and shigellosis at Boston City Hospital. J. Am. Med. Assoc. 229:1309-1312. 3. Marks, M. I., M. Kazemi, and E. MacKay. 1973. In vitro sensitivity of Salmonella to ten antimicrobial agents including sulfamethoxazole and trimethoprim, alone and in combination. Antimicrob. Agents Chemother. 4:555-559. 4. Olarte, J., and E. Galindo. 1973. Salmonella typhi resistant to chloramphenicol, ampicillin, and other antimicrobial agents: strains isolated during an extensive typhoid fever epidemic in Mexico. Antimicrob. Agents Chemother. 4:597-601. 5. Overturf, G., K. I. Marton, and A. W. Mathies, Jr. 1973. Antibiotic resistance in typhoid fever. N. Engl.
J. Med. 289:463-465.
Vol. 11, No. 6 Printed in U.S.A.
In Vitro Antibiotic Susceptibility of Salmonellae FACELUCIA BARROS, OKSANA M. KORZENIOWSKI, MERLE A. SANDE,* KATIA MARTINS, LUIZ CARLOS SANTOS, AND HEONIR ROCHA Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22901,* Department of Medicine, Federal University ofBahia, Salvador, Bahia, Brazil, and Couto Maia Hospital, Salvador, Bahia, Brazil. Received for publication 27 January 1977
In vitro antibiotic susceptibilities were determined for 101 strains of salmonellae. Resistance to chloramphenicol and ampicillin was low. Cefamandole was active against the majority of strains and deserves further evaluation.
The recent identification of chloramphenicol BLP-1761 (an ester of hetacillin, Bristol Laboand multiple drug-resistant salmonella epi- ratories, Syracuse, N.Y.). An inoculum of 104 demics has generated increased interest in the organisms was added to each tube. After 24 h of overall drug sensitivities of these organisms in incubation, samples were taken from all tubes various localities as well as a search for alter- with no visible growth and were plated on nate drug therapy when such resistant strains Trypticase soy agar to determine minimum are identified (4, 5). Cefamandole, a new paren- bactericidal concentrations. Strains of S. typhi teral cephalosporin prepared by substitution of (Fig. 1) were, in general, more susceptible to heterocyclic groups on 7-aminocephalosporanic the antimicrobial agents tested than the "nonacid, has been shown to have a marked effect on typhi" strains (Fig. 2). Cefamandole was the a small number of strains of Salmonella typhi most active drug by weight, with 100% of S. in vitro. To evaluate the potential usefulness of typhi strains inhibited by 1.56 gg/ml or less this antibiotic, 101 strains of salmonella, iso- (Fig. la). This is in contrast to other cephalolated in Salvador, Brazil, were tested in vitro to sporins previously tested (1, 2). Ninety-seven a variety of antibiotics currently in use or un- percent of S. typhi strains was inhibited by BLP-1761 at a concentration of 3.1 g.g/ml as der investigation. Strains studied. The 101 strains of salmo- opposed to 90% for ampicillin. Carbenicillin nella used in our evaluations were isolated was the least active of the penicillin derivafrom patients at the Hospital Professor Edgard tives. Chloramphenicol inhibited 97% of S. typhi Santos and the Hospital Couto Maia from 1972 to 1975. Both hospitals are referral centers for strains with concentrations of less than 12.5 patients with suspected or proven typhoid fever gg/ml (Fig. lb). Ninety-three percent of the and other infectious diseases. The salmonella strains was inhibited by 12.5 gg of tetracycline strains were collected randomly in an area per ml. Gentamicin and tobramycin had simiwhere typhoid fever is endemic, and no epi- lar activity with 93% of strains inhibited by a demic outbreak was documented during the concentration of less than 12.5 ,ug/ml. In contrast to S. typhi, the "non-typhi" salperiod of collection. Serotyping was performed on isolation and reconfirmed prior to antibiotic monella strains exhibited in vitro resistance of susceptibility testing. Of 59 strains of group D 30 to 40% to most antibiotics tested. CefamanS. typhi, 53 were recovered from blood, 4 from dole and BLP-1761 again appeared to be quite stools, and 2 from cerebralspinal fluid. Of the active, each inhibiting 70% of strains with conremaining 42 "non-typhi" salmonella strains, centrations of 1.6 ,ug/ml (Fig. 2a). 22 were recovered from blood, and 20 were isoIn this evaluation of 101 strains of salmolated from stool, cerebralspinal fluid, urine, or nella, only a minor emergence of resistant strains to the antibiotics currently utilized in synovial fluid. Antimicrobial testing. The minimum inhibi- the community was noted. High-level resisttory concentration for each drug was deter- ance to chloramphenicol and ampicillin remined by serial twofold dilutions in Trypticase mains in the 2 to 3% range, comparable to the soy broth with freshly prepared solutions of data of Finland et al. (2), but much less than chloramphenicol, ampicillin, carbenicillin, tet- the 16 to 33% range reported in other areas not racycline, tobramycin, gentamicin, cefaman- involved in an epidemic of chloramphenicoldole (Eli Lilly and Co., Indianapolis, Ind.), and resistant strains. 1071
1072
NOTES
ANTIMICROB. AGENTS CHEMOTHER. SALMONELLA TYPHI 100
-- - - - - -- -- ----
/!
so la
I
60
I
I
-C C
!
II
._
0
20
40
'
j
-AMPICKLLN ~~~CARBENICUllN zBPP-1761 20
20 " ! 1 l !
be
/1
-
GENTAMICIN
- -
TETRACYCLINE TOSRAMYCIN
.......
-- CEFAMAND)OLE
- -
CHLORAMPHENICOL
/ 0.19
035
3.
12.5
50
200
0.19
0.75
3.1
12.5
50
200
Concentration of Antibiotic
(Pg/ml) FIG. 1. (a) and (b) show antibiotic susceptibilities of 59 strains of S. typhi.
SALMONELLA NON-TYPHI /
1008
so
I
60 c~~~~~ -
I
1.
i/~ ~
-HOAPEIO
y
-CFMNOE ~~
IL
I HO A PEIO
CEAM ND LEI
0.19
075
3.1
12.5
50
200
Concentration of Antibiotic
(Mg/ml) FIG. 2. (a) and (b) show antibiotic susceptibilities of 42 strains of 'non-typhi" salmonellae.
NOTES
VOL. 11, 1977
Of note is the emergence of aminoglycoside resistance (7%), which has not been seen by other investigators (1-3). This decreased susceptibility to aminoglycosides is also found in the group of "non-typhi" strains, which showed up to 30% resistance to the maximum achievable serum levels. LITERATURE CITED 1. Bissett, M. L., S. L. Abbott, and R. M. Wood. 1974. Antimicrobial resistance and R factors in Salmonella isolated in California (1971-1972). Antimicrob.
Agents Chemother. 5:161-168.
1073
2. Finland, M., C. Garmer, C. Wilcox, and L. Sabath. 1974. Salmonellosis and shigellosis at Boston City Hospital. J. Am. Med. Assoc. 229:1309-1312. 3. Marks, M. I., M. Kazemi, and E. MacKay. 1973. In vitro sensitivity of Salmonella to ten antimicrobial agents including sulfamethoxazole and trimethoprim, alone and in combination. Antimicrob. Agents Chemother. 4:555-559. 4. Olarte, J., and E. Galindo. 1973. Salmonella typhi resistant to chloramphenicol, ampicillin, and other antimicrobial agents: strains isolated during an extensive typhoid fever epidemic in Mexico. Antimicrob. Agents Chemother. 4:597-601. 5. Overturf, G., K. I. Marton, and A. W. Mathies, Jr. 1973. Antibiotic resistance in typhoid fever. N. Engl.
J. Med. 289:463-465.
