Originalia V, M. Young, M. J. Morris, M. R. Moody, S. C. Schimpff, J. W. Gerster, P. H. Wiernik

An Analysis of Group D Streptococci Recovered from Cancer Patients Summary: A total of 4,166 (17.40/0) strains of Group D streptococci were recovered from 27,474 surveillance samples taken from the nose, throat, gingiva, axilla, and rectum of patients at a cancer center. An additional 2,217 strains were recovered from 7,106 urine samples and 58 strains from 5,286 blood samples. Approximately 11% of gingival cultures yielded Group D streptococci. Streptococcus/aecalis was most prevalent, followed by Streptococcus bovis, Streptococcus faecium, Streptococcus avium, Streptococcus equinus, and Streptococcus durans. Six of the 11 premortem blood cultures positive for S. /aecaIis grew other organisms as well, chiefly gram negative bacilli. The seven S. /aecalis recovered from postmortem bloods all occurred together with gram-negative bacilli or yeasts. Abscesses and lesions had recovery rates of 7.9% and 13.20/0, respectively. S. faecium was the Group D streptococcus resistant to the most antibiotics and S. bovis was the most susceptible. Although most strains were only moderately susceptible to penicillinby disc susceptibility tests, minimum inhibitory concentrations of representative strains were in the susceptible range. Ampicillin susceptibilities ranged from 71°/0 to 93%. About half of the S. faecium and S. avium strains were resistant to carbeniciltin, but the other species were more susceptible. Vancomycin, furadantin, and chloramphenicol all had > 82% susceptibilities to Group D streptococci. The widely divergent antibiotic susceptibilities of the Group D streptococci makes their specific susceptibility tests an essential part of optimal patient care.

Introduction Among the microorganisms that colonize m a n and are capable of invading the compromised host, Group D streptococci have a minor, but significant role. These bacteria occur in large numbers in normal h u m a n feces (1, 2), but do not constitute a part of the permanent oral flora in the majority of normal adults (3). However, they may participate in oral infection (4, 5) and tend to persist in that area when patients have diseases of the upper digestive tract (3). Group D streptococci also cause urinary tract infections (6), bacteremias (7, 8), and endocarditis (9, 10, 11). It has been reported that these organisms were recovered from the buccal cavities of 25% of patients with ulcerated malignant tumors of the buccal cavity, larynx, or pharynx, as well as 16% of patients with malignant disease in areas of the body other than the buccal cavity (3). I n the present study, a review of the sources, infected and non-infected, from which these organisms have been recovered from patients at the Baltimore Cancer Research Center is made and the susceptibilities of the strains to ten antibiotics are presented.

Materials and Methods Zusammen/assung: Analyse der aus Krebspatienten isotierten Streptokokken der Gruppe D. 27 474 Probeabstriche aus Nase, Schlund, Zahnfleisch, AchselhShle und Rektum yon Patienten eines Krebszentrums ergaben die Isolation yon insgesamt 4166 ( = 17,4%) Streptokokkenstiimmen der Gruppe D. Weitere 2217 St~imme wurden aus 7106 Harnproben und 58 St~imme aus 5286 Blutproben isoliert. Ann~ihernd 110/0 der Zahnfleischkulturen ergaben Streptokokken der Gruppe D. Streptococcus [aecalis iiberwog, gefolgt yon S. bovis, S. faecium, S. avium, S. equinus und S. durans. Sechs yon elf pr~imortalen, S. faecaIis-positiven Blutkulturen zeigten auch Wachstum anderer Organismen, insbesondere gramnegativer Bakterien. Sieben postmortale Blutproben ergaben S. faecalis zusammen mit gramnegativen Bakterien oder Helen. Bei Abszessen und Verletzungen betrugen die Isolate 7,9% bzw. I3,2%. Als Streptococcus der Gruppe D erwies sich S. faecium gegentiber den meisten Antibiotika resistent und S. bovis am empfindlichsten. Obwohl sich im Btiittchentest die meisten Stiimme nur als m~iBigPenicillimempfindlicherwiesen, lag die minimale Hemmkonzentration repriisentativer Stiimme im empfindlichen Bereieh. Die Empfindlichkeit gegen Ampicillin schwankte zwischen 71 und 93%. Etwa die HNfte der St~imme yon S. faecium und S. avium waren gegen Carbenicillin resistent, doch waren die anderen Spezies empfindlicher. Bei Vancomycin, Furadantin und Chloramphenicol lag die Empfindlichkeit yon Streptokokken der Gruppe D tiber 82%. Die breite Streuung der Empfindlichkeit yon Streptokokken der Gruppe D liigt ihre spezifische Testung zum wesentlichen Bestandteil opfimaler Patientenbetreuung werden.

98

Infection 6 (1978) Nr. 3

Patient population: The Baltimore Cancer Research Center admits patients with advanced metastaic tumor, lymphoma, and leukemia for radiation therapy, chemotherapy, or both. Patients requiring surgery as the primary form of therapy are not accepted. During the period of study (October 1, 1973 to July 1, 1977), 209 patients with leukemia, 242 with lymphoma, and 419 with solid tumor were admitted. Leukemia patients were placed on oral non-absorbable antibiotics consisting of gentamicin, vancomycin, and nystatin to suppress their intestinal flora during the period of granulocytopenia. Source: Group D streptococci were recovered from surveillance cultures taken twice weekly from the nose, gingiva, axilla, and rectum of all patients with leukemia and from all patients within the Intensive Care Unit of the Baltimore Cancer Research Center. Other patients had surveillance samples taken twice during the frst week of admission. Diagnostic clinical specimens were cultured as indicated by the physician's request. Cultural methods and identification: Isolation of the Group D streptococci evaluated in this study were from 5% rabbit blood agar plates and phenylethyl alcohol plates which were used for the initial plating of samples, as well as for subReceived: 13 January 1978 Dr. V. M. Young, M. J. Morris, B. S., M. R. Moody, M. S., Dr. S. C. Schimpff, P. H. Wiernik, Clinical Oncology Branch, Baltimore Cancer Research Center, National Cancer Institute, University of Maryland Hospital, 22 South Greene St., Baltimore, Maryland 21201, USA.

V. M. Young et al.: Group D Streptococci in Cancer Patients cultures of growth from liquid media. The method of Facklam (12) was used to differentiate the species; Streptococcus fae-

calis, Streptococcus faecium, Streptococcus durans, Streptococcus casseliflavus, Streptococcus avium, Streptococcus bovis, and Streptococcus equinus. Laboratory policy is to speciate all morphologically distinct isolates as to genus and species whether recovered from the surveillance cultures of the nose, throat, gingiva, and axilla or from clinical diagnostic samples. Also, those strains recovered from the first two admission rectal samples and from urines with colony counts > 5 × 104/ml were speciated; other strains from these latter two sources were classified as Group D streptococci.

Susceptibility tests: Susceptibility of the freshly isolated strains to ten antibiotics was deteiTnined by the method of Bauer et al. (13). Ca++ and Mg++ were added to the MuellerHinton agar to bring the ion concentrations to 75 mg and 30 my/liter, respectively (14) and 50/0 hemoglobin added to allow adequate growth. The isolates were tested for susceptibility to penicillin, ampicillin, erythromycin, cephalothin, tetracycline, chloramphenicol, vancomycin, furadantin, gentamicin, and carbenicillin. Minimum inhibitory concentrations (MIC) were done by the method of MaeLowry et al. (15).

Data handling system: All final culture results were handled and stored by use of the computer systems described by VermeuIen et al. (16). Data was retrieved and collated by computer programs written for that purpose.

Results Total Group D streptococci recovered: Of a total of 27,474 surveillance samples taken during the period of study, 4,166 (17.4o/0) yielded Group D streptococci. A n additional 2,217 strains were recovered from diagnostic clinical and autopsy specimens. The number and percent of isolates and the sources from which they were recovered are shown in Table 1. As expected, the percent found in rectal cultures was high (33.5o/0), followed by urine cultures (25.6~/0), gingiva (11.10/0), lesions (10.40/0), and throat (7.1%). Less than 5 % of the samples from other sources yielded Group D streptococci.

Surveillance samples: The percentages of Group D streptococci recovered from the surveillance cultures of patients with lymphoma, leukemia, and solid tumor are shown in Table 2. As can be seen, there were no differences in the frequencies of these organisms recovered from the samples taken from patients who had the various types of neoplasms, with the exception of higher numbers found in the rectal cultures of solid tumor patients than in leukemia patients. S. faecalis, reported as the most prevalent species recovered from "English, Scots, and Americans" (17), was most frequently found, followed by S. bovis, S. faecium, S. equinus, S. durans, and S. avium. S. equinus was not grown from any of the nose cultures. Although the rates for rectal cultures shown in the table represent only the results from the first two cultures taken, relative frequencies of recovery of the various

Table 2: Percentages of Group D streptococci recovered from

surveillance cultures of cancer patients.

Total number of cultures St2 Ly2 Lks

Nose

Gingiva

Axilla

Rectum1

1224 1086 3593

1352 1218 5058

1191 1030 3482

1324 1260 5656

6.5 3.7 3.3

4.7 3.9 4.4

2.2 3.3 2.3

9:4 4.8 2.5

0.4 0.3 0.3

0.3 0.5 0.7

0.5 0.5 0.1

0.8 0.5 0.3

0.2 0 0.03

0.3 0 0.~

0 0.I 0

0.08 0 0.04

0.25 0.3 0.06

1.5 1.1 0.8

0.5 0.1 0.06

1.4 1.0 2.6

0 0 0

0.6 0.3 0.3

0.2 0.1 0

0.2 0.2 0.02

0 0.1 0,06

0.1 0,1 0.1

0,1 0 0.6

0.6 0.2 0.1

S./aecalis St Ly Lk

s. faecium St Ly Lk S. dgraFIs

Table 1: Total Group D streptococci recovered 1.

Source

Total cultures taken

Total no. positive cultures

Percent positive

Nose Gingiva Throat s Axilla Rectum Urines Lesions Bloods Lung4 Spleen4 Liver4

5903 7628 1623 4921 8260 7106 1118 5286 18083 601 720

291 844 116 268 2770 1816 116 26 38 14 t2

4.9 11.1 7.1 5.4 33.5 25.6 10.4 0.5 4.2 2.3 1.7

St Ly Lk

S. bovis

Includes non-speciated Group D streptococci. z Includes surveillance and diagnostic samples. 3 Includes premortem and postmortem bloods. 4 Postmortem samples. 5 Includes right and left lower lobe samples from the same patient; percent positive is based on 904 patients' lung samples.

St Ly Lk

S. equinus St Ly Lk

S. avium St Ly Lk

1 Only the first two admission cultures speciated. 2 St = solid tumor patients; Ly = lymphoma patients; Lk = leukemia patients. Note: Percentages based on total cultures taken.

Infection 6 (1978) Nr. 3

99

V. M. Young et al.: Group D Streptococci in Cancer Patients species of Group D streptococci from rectal samples to one another accurately reflect findings at the time of admission. The only species, other than S. faecatis, with recovery rates above 1% was S. boris isolated from rectum and gingival cultures from which 0.8 to 2.6% were positive. Only a small number of cultures contained more than one species of Group D streptococci.

Diagnostic Samples Blood: As shown in Table 3, a total of 26 blood cultures (0.5%) grew Group D streptococci; nineteen of these were from blood ,drawn prior to death and the other seven from autopsy blood cultures. Many of the blood cultures from which Group D streptococci were grown yielded other organisms as well. Half of the premortem blood cultures positive for S. faecalis grew this organism alone; six yielded S. [aecatis together with gram negative rods and one grew S. faecalis with both gram negative rods and gram positive cocci. The three blood cultures positive for S. ]aecium and the one positive for S. durans grew these organisms as the sole bacterial species present, but the culture which yielded S. boris had Staphylococcus aureus as well. The only Group D streptococcus recovered from autopsy blood cultures was S. faecalis (seven samples) and all occurred together with gram negative bacilli; one of these samples grew Candida albicans and Torulopsis glabrata as well. None of the patients from whose blood cultures Group D streptococci were recovered had endocarditis.

Throat: Most of the throat cultures were taken from patients with pharyngitis. Although S. /aecalis was considerably more prevalent than other species of Group D streptococci in the surveillance cultures, there was no significant difference between the number of S. faecalis and S. bovis recovered from the diagnostic throat cultures (Table 3). S. avium was grown from the throat specimens of three patients (only two S. avium strains were recovered from all other clinical samples); the two S. equinus strains recovered were grown from the throat cultures of solid tumor patients. No S. durans grew from premortem diagnostic samples. Most throat cultures, not unexpectedly, had multiple organisms isolated so that it was usually difficult, if not impossible, to associate a specific organism as an etiologic agent of infection as opposed to colonization at the site of infection. Urine: The percent of each species of Group D streptococci shown in Table 3 does not reflect the total number recovered from urine samples (26.20/0), as only those with colony counts of _> 5 × 10~ were speciated. This high frequency of urine samples with low numbers of Group D streptococci is a result of our laboratory policy of listing MI organisms regardless of quantitation and is an indication of the frequent difficulty of aseptic collection of urine in seriously ill patients. As expected, S. [aecalis was predominant among the speciated strains with approximately 5 % of urines from solid tumor patients yielding this organism; patients with ba'nphoma (2.7°/0) and leukemia (1.70/0) yielded slightly less. S. faecium and S. boris were recovered and speciated in very few cases.

Table 3: Percentages of Group D streptococci recovered from clinical samplesk

S. [aecalis

Total number of cultures Source

St~

Ly~

Lk~

St

Ly

S. faecium Lk

St

Ly

S. bovis Lk

Total

St

Ly

Lk

positive

%

19

0.4

Premortems 741

1074

2875

1.5

0

0

0

214

351

1058

1.4

1.1

3.0

0

0

0.2

0.9

0.85

0.95

117

7.2

1903

2153

3050

4.8

2.7

1.7

0. i

0.1

0.03

0.1

0.02

0.03

1864

26.2

Abscess

53

53

161

1.9

3,8

1.9

0

1.9

0.6

0

0

0

21

7.9

Lesion

147

159

545

8.2

12.0

3,9

0

0

0.6

1.4

0.6

0.6

112

13.2

Blood Throat 3 UrinO

.02

.07

0

.09

.07

Postmortems Blood

274

97

225

0.4

1.0

2.2

0

0

0

0

0

0

7

1.2

Lung

834~ 303

341 73

633 225

2.2 1.6

1.2 0

2.2 2.2

0.2 0.3

0.3 0

0.6 0

0,5 0

0.3 0

0.1 0

39 14

4.3 2.3

313

168

239

1.0

0.6

1.3

0

0

0

0

0

0

12

1.7

Spleen Liver

S. boris was recovered from 1 patient with mycosis fungoides; S. durans was recovered from the spleen and liver of one patient with solid tumor at autopsy and from 1 premortem blood; S. equinus was recovered from the throat of one patient with solid tumor and the right and left lower lobe of another at autopsy; S. avium was recovered from the throat of one patient each with lymphoma and leukemia, in the urine of another lymphoma patient, and in a lesion of a leukemia patient. St = solid tumor patients, Ly = Iymphoma patients, Lk = leukemia patients, Throat cultures consist of surveillance and clinical samples; chiefly clinical. 4 Group D streptococci were speciated only when CFU ~ 5 × 104. Numbers of cultures include right and left lower lobe samples from the same patients; percent positive is based on 417 solid tumor patients, I70 lymphoma patients, and 316 leukemia patients,

100

Infection 6 (1978) Nr. 3

V. M. Young et al.: Group D Streptococci in Cancer Patients Lesions and abscesses: The higher percentage of S. faecalis than other Group D streptococci recovered from cultures of lesions may be accounted for by their general prevalence and by the frequency of perianal and perirectal lesions among this patient population. However, it does not account for the higher frequency in patients with lymphoma (12.0o/0) as compared to those with leukemia (3.90/0). Other species of Group D streptococci either were not found in lesions and abscesses or had a very low recovery rate. Postmortem samples: Recovery of Group D streptococci from autopsy samples was low, a clear indication of their limited pathogenic potential. A few strains of S. equinus, S. bovis, and S. faecium were found, chiefly in samples of lung tissue taken at autopsy, otherwise only low numbers of S. faecalis were grown. Percent species o/ Group D streptococci recovered: It is of interest that while S./aecalis is far more prevalent in this patient population than other species of Group D streptococci, its prevalence in samples taken from various sources varied widely (Table 4). S. bovis did not comprise many of the strains from the nose (3.8%), but was disproportionately higher in gingival (15.0o/o), throat (25.40/0), and autopsy lung cultures (11.50/0). On the other hand, S. faecium was disproportionately higher in perianal and perirectal lesions, as well as in blood and lung cultures. But few of the high urine counts were accounted for by Group D streptococci other than S. faecatis (92.7o/0). Table 4: Group D streptococci recovered from cultures; percent o] each speeiesk

Source

No. of

~

.~

~

~

.~

isolates

~

~

.~

,~

~

"~

Nose

212

84.9

8.5

1.4

3.8

0

1.4

Gingiva

492

67.5

9.1

1.2

15.0

5.3

1.8

Axilla

151

82.1

9.9

0.7

3.3

2.0

2.0

0.8

12.2

Rectum

369

72.1

8.9

Abscess

8

75.0

25.0

0

0

Lesion Blood ~

61

83.6

9.8

0

1.6

80.7

4.9 11.5

0

26

3.8

3.8

0

0

Throat

59

66.1

3.4

0

25.4

Urine

218

92.7

2.7

0

3.7

1.3

4.6

0

0

3.4

1.7

0

0.9

Discussion Hugh et at. (3) in 1959 reported that Group D streptococci were more prevalent in the buccal cavity of cancer patients, who may or may not have had ulcerated malignant neoplasms located in that area, than in the buccal cavity of normal adults. The present study includes patients who had malignant neoplasms, though few were

Lung3

26

69.2

13.4

0

11.5

5.7

0

LiverZ

8

87.5

0

12.5

0

0

0

Spleen 3

12

83.3

8.3

8.3

0

0

0

1 Non-speciated Group D streptococci excluded. Includes premortem and :postmortem bloods. 3 Postmortem samples. Note: Only one S. casseliflavus was recovered.

Antibiotic susceptibilities: The antibiotic susceptibilities of these Group D streptococci to ten antibiotics are shown in Table 5. Penicillin was clearly not an effective drug f o r the enterococci according to results obtained with the disc susceptibility tests; i. e., only 200/0 of S. faecalis, 16% of S. faecium, 390/0 of S. durans, and 170/0 of S. avium were susceptible to this agent, whereas 74o/0 of S. equinus and 64% of S. bovis strains were susceptible. As the majority of S. faecalis, S. faecium, S. avium, and S. durans gave results in the moderately susceptible range, it was decided to determine the minimum inhibitory concentration of a group of thirty of these strains by use of the microtiter technique (15). AII of the thirty MIC's gave results of 6.25 or 12.5 mcg/ml which were clearly within the susceptible range. Repeat disc susceptibility tests were then performed on trypticase soy agar* and in no instance were the zone size differences sufficient to change the intermediate susceptibility results. In contrast, carbenicillin appears to be more efficacious. Eighty-eight percent of S. equinus and all S. durans were susceptible and about 790/0 of S. faecalis and S. bovis were also susceptible. However, only half of the S./aecium strains and 57°/o of the S. avium strains were susceptible to carbenicillin. Susceptibility of S. ]aecatis, S. bovis, and S. equinus strains to ampicillin was 85% or above, whereas that of other species was lower. Susceptibility to erythromycin did not vary significantly from the susceptibility to carbenicillin, although that of S. durans was somewhat lower at 85%. The aminoglycoside, gentamicin, was generally effective against the prevalent Group D streptococci, S. faecaIis (86°/0) and S. bovis (89%), but ranged as low as 410/0 for S./aecium. Vancomycin, in contrast, had a range of susceptibilities from 85% for S. equinus to 1000/0 for S. durans. This antibiotic and chloramphenicol (lowest susceptibility rate, 92~/0) were the two most effective antibiotics as determined by disc susceptibility tests. Neither cephalothin nor tetracycline were active against a majority of the Group D streptococci tested. It can also be noted in Table 5 that S. faecium showed resistance to more antibiotics than any of the other species of Group D streptococci studied. Only three antibiotics, furandantin, chloramphenicol, and vancomycin inhibited 870/0 or more of these strains; ampicillin inhibited 71.20/0 of the strains and the other antibiotics, 50% or less. The next most resistant species was S. avium, but the most prevalent species, S. faecalis, was susceptible to most of the generally used antimicrobial agents.

* Difco Laboratories, Detroit, Michigan 48232, U.S.A.

Infection 6 (1978) Nr. 3

101

V. M. Young et al.: Group D Streptococci in Cancer Patients Table 5: Percentages o/antibiotic susceptibilities of Group D streptococci.

Streptococcus spp.

Susceptibility

Penicillin

Carbenicillin

Ampicillin

Erythromycin

Gentamicin

S. faecaIis

S* MS* R*

20.0 70.7 9.2

79.2 12.9 7.8

84.7 11.2 4.1

79.6 6.3 14.0

86.4 7.5 6.0

Total no. tested

S. faecium

S MS R Total no. tested

S. boris

S MS R Total no. tested

S. avium

57 MS R Total no. tested

S. equinus

S MS R Total no. tested

S. durans

S MS R Total no. tested

615

16.7 43.9 39.4 66

64.4 20.7 14.9 87

16.7 50.0 33.3 30

74.1 18.5 7.4 27

38.5 53.8 7.7 13

612

50.0 7.6 42.4 66

78.8 8.2 12.9 85

56.7 6.7 36.6 30

88.9 3.7 7.4 27

100.0 0 0 13

615

71.2 9.1 19.7 66

88.5 6.9 4.6 87

76.7 10.0 13.3 30

92.6 0 7.4 27

3d.9 15.4 7.7 13

613

612

43.1 3.1 53.8

40.9 13.6 45.5

65

66

80.2 12.8 7.0

89.3 2.4 8.3

86

84

63.3 13.3 23.3

76.7 3.3 20.0

30

30

96.3 0 3.7

81.5 0 18.5

27

27

84.6 7.7 7.7

53.8 7.7 38.5

13

13

Vanco- Chloram- Cephalmycin phenicol othin 98.2 0.3 1.5 613

I00.0 0 0 66

97.7 0 2.3 87

93.3 0 6.7 30

85.2 3.7 11.1 27

100.0 0 0 13

93.6 5.0 1.3 614

98.5 1.5 0 66

94.2 4.6 J.2 86

100.0 0 0 30

100.0 0 0 27

92.3 7.7 0 13

9.9 21.0 69.1 609

I2.3 7.7 80.0 65

62.4 9.4 28.2 85

13.3 13.3 73.3 30

81.5 11.1 7.4 27

61.5 23.1 15.4 13

Tetracycline

Furadantin

35.2 2.4 62.4

96.1 1.9 1.9

614

56.1 0 43.9 66

50.0 4.7 45.3 86

20.0 3.3 76.7 30

66.7 3.7 29.6 27

53.8 7.7 38.5 13

516

86.8 5.7 7.5 53

90.8 5.3 3.9 76

96.2 3.8 0 30

81.5 3.7 14.8 27

92.3 0 7.7 13

* S = susceptible; MS = moderately susceptible; R = resistant. found in the oral cavity; however, minor oral lesions in these patients were not an u n c o m m o n occurrence. Under these conditions, 11% of the 7,628 gingival cultures yielded Group D streptococci. S. faecalis comprised 7 % of the total Group D streptococci recovered from cultures of this area. Although Bahn et al. (17) have reported that as many as 23.1% of dental clinic patients had Group D streptococci in their saliva, only 3.60/0 of samples from normal naval recruits had these organisms, a rate similar to the 40/0 reported by Hugh et al. (3) and the "low numbers" of N o r d and Wadstr6m (5). Socransky (18) found most of the oral enterococci in the gingivaI crevice. It is apparent that a variety of events which affect the oral microbiota can give rise to an increased number of Group D streptococci in the oral cavity. Although depressed gastric acidity appears to play a rote in creating

102

InLection 6 (1978) Nr. 3

a favorable environment for colonization of the oral cavity with Group D streptococci (3), other factors which are little understood undoubtedly contribute. Furthermore, the effects of the antineoplastic agents and antibiotics on the oral microbiota are not known. Not only was the Group D streptococcus gingival carrier rate high in the patients with neoplastic disease, the nose and axilla harbored these organisms, as well. Approximately 5 % of the surveillance cultures from the latter sites also yielded Group D streptococci. However, the percent of rectal cultures that had these organisms present did not appear to be different from normal carrier rates (33.50/0). Nor did there appear to be differences in the recovery of Group D Streptococci from the surveillance cultures of solid tumor, tymphoma, or leukemia patients with the exception of rectal cultures. Undoubtedly, the

V. M. Young et al.: Group D Streptococci in Cancer Patients oral non-absorbable antibiotics given to leukemia patients to suppress their enteric flora accounts for the low recovery rate from rectal cultures in this group of patients. Although the carrier state in normal individuals is reported usually to be transistory, many of the cancer patients in this study have had repeated sets of surveillance cultures that grew Group D streptococci. It also was not uncommon that different species were recovered from different sites of the same individual or that a transient species, different from the one colonizing a particular site, could also be present. The species of Group D streptococci which are not considered to be enterococci; i. e., S. boris, S. equinus, and S. avium, were all recovered from the cancer patients, but in very low numbers. All had surveillance culture recovery rates of less than 10/0 except S. bovis, which was present in 1 to 2 % of the gingival cultures. One patient developed bacteremia caused by S. bovis, but no endocarditis, as described by Ravreby et al. (I9), occurred. Most striking is the predilection of this species of Group D streptococci for the gingiva and throat where it comprises 15 and 25%, respectively, of the Group D streptococci recovered. S. avium and S. equinus, which are not generally reported from human sources, had very low recovery rates and when present, were generally found in gingival or rectal surveillance cultures. Of the enterococci, S. faecium has been reported to be more prevalent than S./aecalis in human hosts of several European countries (20), but was less common in the cancer patients in this study as was true for normal adults in the United States (19). S. faecium was slightly less commonly recovered than S. bovis, as well. Nevertheless, this species was recovered from the blood of three patients and comprised 25% of the Group D streptococci recovered from abscesses and 13'0/0 of those from autopsy lung samples. The pathogenic potential of this species, when it does occur, gains significance from the fact that it was resistant to more antibiotics than any of the other species of Group D streptococci tested. It had satisfactory rates of susceptibility only to vaneomycin (100%), chloramphenicol (98.5o/o), and furadantin (86.7o/0). Group D streptococci are generally reported to be susceptible to penicillin (9, 20, 21, 22). In the present study, the majority of S. bovis (64.4'o/0) and S. equinus (74.10/0) strains were clearly susceptible to penicillin by the disc susceptibility test. However, the majority of the other Group D streptococci gave results with the disc susceptibility tests in the intermediate range to penicillin. It was further demonstrated that this occurred when the MIC's were 6.25 to 12.5 U/ml. ff penicillin is under consideration for therapy of infections caused by the latter Group D streptococci, it is clear that reliance should not be placed on the disc test for determination of susceptibility. Ampicillin was effective against a majority of the Group D streptococci strains studied (71.2 to 92.6% , dependent upon the species) as reported by other investigators (11).

CarbeniciUin, another penicillin-derivative, varied greatly in in vitro activity against Group D streptococci. Approximately 79% of the two most commonly encountered species, S. faecatis and S. bovis, were susceptible. The other species were more resistant. Most investigators recommend that penicillin or ampicillin be used only in combination with other antimicrobial agents (23); e.g., gentamicin (21, 24, 25, 26, 27, 28), streptomycin (25, 26), or tobramycin (28). It has been reported that a high proportion of the Group D streptococci have reduced susceptibility to some of the aminoglycoside antibiotics (24, 29, 30, 3i). Gentamicin susceptibilities in the present study varied from a high of 890/0 for S. bovis to a low of 410/0 for S. faecium. Of the 615 strains of S. faecalis tested against gentamicin, 86°/0 were susceptible; however, 370/o of the strains recovered in 1976 were resistant to this antibiotic. Vancomycin, a drug which has also been recommended for use in combined antibiotic therapy (25, 31) was highly inhibitory to all species of Group D streptococci tested. The least susceptible species was S. equinus and even this rare species was 850/o susceptible. Chloramphenicol was a highly effective antibiotic against all of the Group D streptococci in the in vitro tests. Neither cephalothin nor tetracycline were effective against this group of organisms. Antibiotic susceptibilities of the more resistant species of the Group D streptococci are widely divergent from those which are more susceptible, and combined therapy remains a valid approach only when tests with the infecting strain reveals that it is not resistant to the antibiotics selected. Therefore, determination of the specific susceptibility of an infecting strain becomes an essential part of optimal patient care.

Literature 1. Bartley, C. H., Slanetz, L. W.: Types and sanitary significance of fecal streptococci isolated from feces, sewage and water. Am. I. Public Health 50 (1960) 1545-1552. 2. Kenner, B. A., Clark, F., KabIer, P. W.: Fecal streptococci. II. Quantitation of streptococci in feces. Am. J. Public Health 50 (1960) 1545-1552. 3. Hugh, R., Klopp, C. T., Ryschenkow, E.: The increased incidence of enterococci in the buccal cavity in the presence of disease. Med. Ann. D. C. 28 (1959) 61-67. 4. MolIer, A. J. R.: Microbiological examination of root canals and periapical tissues of human teeth. Akademifodaget, Goteberg, 1966. 5. Nord, Carl-Erik, Wadstrom, T.: Characterization of haemolytic enterococci isolated from oral infections. Acta Odontol. Scand. 31 (1973) 395-399. 6. Freedman, L. R.: Pyelonephritis and urinary tract infection. In: Diseases of the kidney (Ed.: M.B. Strauss, L. G. Welt), p. 69. Little, Brown and Co., Boston, 1963. 7. Bengtsson, E., StrandelI, T., Svanborn, M., Tunevall, G.: Azidocillin treatment of enterococcal septicemia. Scand. J. Infect. Diss. 4 (1972) 143-148.

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V. M. Young et al.: Group D Streptococci in Cancer Patients 8. Ravreby, W. D., Bottone, E, 1., Keusch, G. T.: Group D streptococcal bacteremia, with emphasis on the incidence and presentation of infections due to Streptococcus boris. N. Engl. J. Med, 289 (1973) 1400-1403. 9. Thornsberry, C., Bake,, C. N., Facklam, R. R.: Antibiotic susceptibility of Streptococcus boris and other Group D streptococci causing endocarditis. Antimicrob. Ag. Chemother. 5 (1974) 228-233. 10. Cherubim, C. E., Neu, H. C.: Infective endocarditis at the Presbyterian Hospital in New York City from 1938-1967. Am. I. Med. 51 (1971) 83-96. 11. Beaty, H. N., Turck, M., Petersdorf, R. G.: Activity of broad-spectrum antibiotics against enterococci and their efficacy in enterococcal endocarditis. Ann. N. Y. Acad. Sci. 145 (1967) 464-471. 12. Facklam, R. R.: Recognition of Group D streptococcal species of human origin by biochemical and physiological tests. Appl. Mierobiol. 23 (1972) 1131-1139. 13. Bauer, A. W., Kirby, M. M., Sherris, 1. C., Turck, M.: Antibiotic susceptibility testing by a standard single disc method. Am. I. Clin. Pathol. 43 (1966) 493-496. 14. Relier, B. L., Schoenknecht, F. D., Kenny, M. A., Sherris, J. C.: Antibiotic susceptibility testing of Pseudomonas aeruginosa: Selection of a control strain and criteria for magnesium and calcium content in media. J. Infect. Dis. 130 (1974) 454-463. 15. MacLowry, J. D., Jaqua, M. J., Selepak, S. T.: Detailed methodology and implementation of a semi-automated serial dilution microtechnique for antimicrobial susceptibility testing. Appl. Microhiol. 20 (1970) 46-53. 16. VermeuIen, G. D., Gerster, J. W., Young, V. M., Hsieh, R. K. C.: A computerized data storage and retrieval system for clinical microbiology. Am. J. Clin. Pathol. 61 (1974) 209-2t 5. 17. Bahn, A. N., Shklair, L., Mazzarella, M., CaIandra, .L C.: Incidence of oral Group D streptococci. J. Dent. Res. 39 (1960) 686-687. 18. Socransky, S. S.: Relationship of bacteria to the etiology of peridontal disease. J. Dent. Res. 49 (1970) 209-222. 19. Ravrebry, W. D., Bottone, E. J., Keusch, G. T.: Group D streptococcal bacteremia, with emphasis on the incidence and presentation of infections due to Streptococcus boris. N. Engl. J. Med. 289 (1973) 1400-1403.

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20. DeibeI, R. H.: The Group D streptococci. Bacteriol. Rev. 28 (1964) 330-366. 21. Watanakunakorn, C., Glotzbecker, C.: Synergism with aminoglycosides of penicillin, ampicillin, and vancomycin against non-enterococcal Group D streptococci and ~5ridans streptococci. L Med. MicrobioI. 10 (1977) 133-138. 22. Toala, P., McDonald, A., Wilcox, C., Finland, M.: Susceptibility of Group D streptococcus (enterococcus) to 21 antibiotics in vitro, with special reference to species differences. Am. L Med. Sci. 258 (1969) 416-430. 23. Washington, J. A. I1, Herman, P. E., Martin, W. J.: In vitro susceptibility of staphylococci and streptococci and influence of agar media on minimum inhibitory concentration. Mayo Clin. Proc. 45 (1970) 527-535. 24. Standiford, H. D., de Maine, ]. B., Kirby, W. M. M.: Antibiotic synergism of enterococci. Arch. Intern. Med. 126 (1970) 255-259. 25. Harwick, H. J., Kalmanson, G. M., Guze, L. B.: In vitro activity of ampicillin or vancomycin combined with gentamicin or streptomycin against enterococcL Antimicrob. Ag. Chemother. 4 (1973) 383-387. 26. Watanakunakorn, C.: Penicillin combined with gentamicin or streptomycin: synergism against enterococci. I. Infect. Dis. 124 (1971) 581-586. 27. Weinstein, A. J., Moellering, R. C.: Penicillin and gentamicin therapy for enterococcal irffections. J. Am. Meal. Assoc. 223 (1973) 1030-1032. 28. Moellering, R. C., Jr., Wennersten, C., Weinstein, A. J.: Penicillin-tobramycin synergism against enterococci: a comparison with penicillin and gentamicin. Antimicrob. Ag. Chemother. 3 (t973) 526-52% 29. Basker, M. J., Slocombe, B., Sutherland, R.: Aminoglycoside-resistant enterococci. J. Clin. Pathol. 30 (1977) 375-380. 30. Calderwood, S. A., Wennersten, C., MoelIering, R. C., lr., Kuntz, L. J., Krogstad, D. J.: Resistance to six aminocyclitol antibiotics among enterococci: prevalence, evolution and relationship to synergism with penicillin. Antimicrob. Ag. Chemother. 12 (1977) 401-405. 31. Moellering, R. C., Jr., Wennersten, C., Medrek, T., Weinberg, A. N.: Prevalence of high level resistance to aminoglycosides in clinical isolates of enterococci. Antimicrob. Ag. Chemother. 1970 (1971) 335-340.

An analysis of group D streptococci recovered from cancer patients.

Originalia V, M. Young, M. J. Morris, M. R. Moody, S. C. Schimpff, J. W. Gerster, P. H. Wiernik An Analysis of Group D Streptococci Recovered from Ca...
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