Recurrence of group B streptococcal infection

August 1976 TheJournalofPEDIATRICS

183

Recurrence of group B streptococcal infection It is clear that the group B streptococcus has become a major pathogen of young infants within the comparatively recent past. Further it is clear that, as with other endemic and epidemic pathogens, increasing clinical and laboratory experience brings to light variations not initially evident. In addition, therapy presumably effective in initial cases may not continue to be so. The following papers by coincidence were received over a relatively brief period of time. Hence, for emphasis of some of the problems related to this organism, they are presented as a group.

Editor

Daniel D. Broughton, M.D., Wendy G. Mitchell, M.D., Moses Grossman, M.D.,* W. Keith Hadley, M.D.,

and Martin S. Cohen, M . D . , S a n Francisco, C a l i f

INFECTIONS caused by g r o u p B streptococcus h a v e recently b e c o m e a m a j o r cause of n e o n a t a l sepsis? Recurrences of GBS are infrequent, a l t h o u g h Tseng a n d Kandall=' r e p o r t e d a confirmed recurrence in one i n f a n t and a GBS infection following a group D infection in another child, each of w h o m had n o r m a l cellular a n d h u m o r a l i m m u n i t y . We n o w report a n i n f a n t w h o survived n e o n a t a l sepsis with GBS after t r e a t m e n t with ampieillin, but w h o h a d a recurrence.

CASE REPORT This 3,100-gm male was born to a healthy 30-year-old, gravida 2, para 1, abortus I, whitemother following an uncomplicated term gestation. Membranes ruptured 26 hours prior to delivery and Pitocin was administered intravenously. Cervical culture obtained from the mother six weeks postpartum did not grow GBS, and the mother had remained afebrile in the interim. The infant's Apgar scores were 9 and fl0 at one and five minutes, respectively. Cultures were obtained at birth of the skin, cord, cord blood, and fetal side of the placeri,ta. At four hours of age, a weak suck and cardiovascular instability were noted and samples of blood, cerebrospinal fluid, and urine were obtained for further culture. Examination of the CSF revealed 3 white blood cells and 320 red blood cells per high-power field, glucose

From the Departments of Pediatrics and Laboratory Medicine, San Francisco General Hospital, and University of California School of Medicine, San Francisco, and Letterman General Hospital *Reprint address: Department of Pediatrics, San Francisco General Hospital, San Francisco, Calif."94110.

30 mg/dl, and blood glucose 42 mg/dI. The initial chest roentgenogram showe~ a right middle lobe pneumonia; cultures of skin, cord, placenta, blood, and urine all grew GBS, serotype III. CSF and cord blood were sterile. Ampicillin (200 mg/kg/day intravenously) and kanamycin (15 mg/kg/day intramuscularly) were administered with clinical improvement after two days. This was changed to intravenous ampicillin only (200 mg/kg/day) to complete a 10-day course. The pneumonia Cleared and he became asymptomatic. Thirty-six hours after the last dose of ampicillin, cultures of blood and CSF were sterile. He was discharged from the hospital at 12 days of age.

Abbreviations used GBS: group B streptococcus CSF: cerebrospinal fluid He returned to the Emergency Room six days later with a temperature of 103 ~ F. Examination of the CSF revealed 2 white blood cells (both mononuclear) and 16 red blood cells per highpower field. Culture of blood grew GBS but CSF was sterile. The patient was readmitted to the hospital at 20 days of age (eight days after discharge) in a lethargic state. Physical examination was unremarkable except for a Grade 3/4 systolic murmur. Chest roentgenogram and electrocardiogram were normal. Examination of the CSF revealed 1,200 red blood cells/ mm a and 31 white blood cells/ruraL Repeat blood and CSF cultures taken prior to treatment gre%GBS, serotype III. Ampicillin (400 mg/kg/day intravenously) aild kanamycin (15 mg/kg/ day intramuscularly) were begun, and this was changed to aqueous penicillin (100,000 U/kg/day intravenously) when the results of the second cultures were reported.

184

Group B streptococcal infection

The Journal of Pediatrics August 1976

Table I. S e r u m i n h i b i t o r y a n d bactericidal activity d u r i n g treatment*

Antibiotic regimen Oral penicillin VK 250 mg/kg/day Oral penicillin VK 250 mg/kg/day Oral penicillin VK 250 mg/kg/day and Kanamycin 15 mg/kg/day IM

Time after last dose (hr)

Serum inhibitory activitjf

Serum tidal activity~

4 1/2

1:128

1:4

2

1:512

< 1:2

3 1/2

1:64

1:8

3/4

*The patient's serum was diluted in Mueller-Hinton broth. The inoculum was 10" bacteria/rot from an 18-hour culture. tlnhibitory activity = highest dilution which inhibits visible growth. ~:Bactericidalactivity = highest dilution which kills 99.9% of the inoculum after 24 hours incubation at 35~ C.

T a b l e I1. In vitro susceptibilities o f GBS recovered from patient*

I Penicillin Ampicillin Kanamycin Penicillin "1 Kanamycin f Combined

~f 0.078 u/ml < 0.12/~g/ml > 100 ~g/ml 0.08 u/ml 30 t~g/ml

I

MBC~. 10 u/ml > 8/~g/ml > 100 t~g/ml 0.08 u/ml 30/~g/ml

*Antibiotic dilutions were made in Mueller-Hinton broth. The inoculum was 10~ bacteria/ml from an 18-hour culture. tMinimal inhibitory concentration = lowest antibiotic concentration which inhibits visible growth. :~Minimal bactericidal concentration = lowest antibiotic concentration which kills 99.9%of the inoculum after 24 hours incubation at 35~ C. Both the organism obtained during the initial episode and one obtained during the~recurrent were tested.

Lethargy disappeared gradually, but a variable systolic murmur persisted. A diagnosis of bacterial endocarditis was considered. After two weeks of intravenous thei:apy the infant was given oral penicillin (250 mg/kg/day). Serum bactericidal levels (Table I) and tube dilution susceptibilities (Table II) were obtained. Because of the marked difference between the inhibitory and bactericidal activity, kanamycin (15 mg/kg/day intramuscularly) was added; this combination of oral penicillin and intramuscular kanamycin was continued for two weeks; the serum levels showed good bactericidal activity (Table I). The heart murmur decreased gradually but was still audible as a soft, grade 1/6 systolic murmur at the mid left sternal border at the time of discharge. Blood and CSF cultures drawn 36 to 72 hours after the antibiotics were discontinued were sterile. Since discharge, he has' done well for six months. The Grade 1/6 systolic murmur persists but there is no evidence of heart disease. The GBS recovered during the initial episode and during the

recurrence were both serotype III and had identical antibiotic susceptibilities. DISCUSSION T h r e e possible m e c h a n i s m s m a y explain the recurrence o f GBS in this infant; h e m a y h a v e b e c o m e reinfected; there m a y have b e e n a sequestration o f organisms; or the organism m a y n o t have b e e n fully sensitive to ampicillin. The high colonization rate o f m o t h e r s o f septic infants would suggest that, if reinfection is likely, it w o u l d be seen fairly commonly, yet little m e n t i o n of it is m a d e in the literature. A l t h o u g h the infection m a y not h a v e b e e n eradicated d u r i n g the initial treatment, there were n o clinical signs o f a n abscess or other sequestration o f the o r g a n i s m a n d no signs of osteomyelitis or septic arthritis. T h e c h a n g i n g heart m u r m u r brings u p the possibility o f bacterial endocarditis (possibly in the p a t e n t ductus arteriosus); the patient's clinical course is consistent with this diagnosis? Partially treated endocarditis m a y possibly explain the recurrence o f GBS. G r o u p B streptococcal infections are susceptible to penicillin a n d ampicillin. However, previous studies have listed only m i n i m a l inhibitory c o n c e n t r a t i o n s ? T h e clinical significance of the difference b e t w e e n the inhibitory a n d bactericidal levels in our p a t i e n t ' s GBS is not clear, a l t h o u g h a similar p h e n o m e n o n has b e e n d e m o n s t r a t e d in Listeria monocytogenes by M c C r a c k e n a n d associates? Jawetz a n d Sonne 6 in their review o f bacterial endocarditis, state that the ,minimal inhibitory c o n c e n t r a t i o n for penicillin is of no clinical value in treating group D streptococcal endocarditis. The difference b e t w e e n s e r u m bacteriostatic a n d bactericidal activity while the i n f a n t was receiving penicillin (Table I) led us to p e r f o r m in vitro tube dilution sensitivities for this strain o f GBS ( T a b l e II). Penicillink a n a m y c i n synergism was suggested b y this study. Penicillin-aminoglycoside synergism h a s b e e n d e m o n strated for g r o u p D Streptococcus ~ a n d Listeria ~ b u t not previously for GBS. Synergism b e t w e e n penicillin arid streptomycin has also b e e n s h o w n for viridans streptococci sensitive to penicillin." F u r t h e r e v a l u a t i o n o f the response o f GBS to antibiotics is w a r r a n t e d .

REFERENCES

1. Howard JB, and McCracken GH Jr: The spectrum of Group B streptococcal infections in infancy, Am J Dis Child 128:85, 1974. 2. Tseng P, and Kandall SR: Group B streptococcal disease in neonates and infants, NY State J Med 74:2169, 1974. 3. Johnson DH, Rosenthal A, and Nadas AS: Bacterial endocardifis in children under 2 years of age, Am J Dis Child 129:183, 1975.

Volume 89 Number 2

Group B streptococcal infection

4. Anthony BF, and Concepcion NG: Group B streptococcus in a general hospital, J Infect Dis 123:56!, 1975. 5. McCracken GJ, Nelson JD, and Thomas ML: A comparison of ampicillin and carbenicillin against listeria and enterococcus, Antimicrob Agents Chemother 3:343, 1973. 6. Jawetz E, and Sonne M: Penicillin-streptomycin treatment of enterococcal endocarditis, a re-evaluation, N Engl J Med 274:710, 1966. 7. Jawetz E, and Gunnison JB: Antibiotic synergism and antagonism: Assessment of problem, Pharmacol Rev 5:175, 1953.

18 5

Gordon RC, Barrett FF, and Clark DJ : Influence of several antibiotics, singly and in combination on the growth of Listeria monocytogenes, J PEDIATR 80:667, 1972. Durack DT, Pelletier LL, and Petersdorf RG: Chemotherapy of experimental streptococcal endocarditis. II. Synergism between penicillin and streptomycin against penicillin sensitive streptococci, J Clin Invest 53:829, 1974.

Recurrence of group B streptococcal infection William E. Truog, M.D.,* Roy F. Davis, M.D., and C. George Ray, M.D., Seattle, Wash.

N E O N A T A L group B streptococcal sepsis a n d meningitis constitute m a j o r diagnostic 1 a n d epidemiologic Pr0blems.2.3 Once diagnosed with positive b l o o d a n d cerebrospinal fluid cultures, however, t h e r a p y is relatively specific; crystalline penicillin G is currently r e c o m m e n d e d for 10 to 14 days, a s s u m i n g a p r o m p t clinical r e s p o n s e > 5 If recurrence o f the infection, once p r e s u m a b l y a d e q u a t e ly treated, occurs, it m u s t be quite ~unusual. W e h a v e recently recognized such a case, which constitutes the basis o f this report.

sinus rhythm. Spinal fluid, blood, and urine were cultured. The cerebrospinal fluid contained 1,558 white blood cells/mm 3 with 100% neutrophils (Table I). The blood white cell count was 25,600 cells/mm a with 65% neutrophils and band forms. Therapy with ampicillin and gentamicin was started, but changed to intravenous penicillin G, 150,000 U/kg/24 hr, on Day 2 when the blood and CSF cultures both yielded group B streptococcus. Culture of the mother's vagina was negative for streptococci. Abbreviation used CSF: cerebrospinal fluid

CASE REPORT This 8-day-old white girl was the 3,200-gm product of a 37week uncomplicated gestation and a five-hour uncomplicated labor and delivery. She was well until eight hours prior to admission when transient grunting respirations were noted. Physical examination on admission was normal. A few hours after admission, paroxysmal atrial tachycardia and a fever of 39.5 ~ were noted. Digoxin was begun, promptly re-establishing

From the University of Washington School of Medicine, Department of Pediatrics, and The Children's Orthopedic Hospital and Medical Center. *Reprint address: Departmentof Pediatrics, Universityof Washington, Seattle, Wash 98195.

The patient promptly responded clinically. Serial CSF results are shown in Table I. On Day 10 the patient had a normal physical examination; in light of the CSF findings, however, intravenous penicillin was continued for another four days. Following another three days of observation after discontinuance of antibiotic therapy, with no change in status, the patient was discharged. She remained well at home for four days until six hours before readmission, when fever and irriffibility were noted. Physical examination revealed an irritable child with no focal neurologic findings. The CSF contained 1,685 white blood cells/mm ~ with 73% neutrophils; the blood white cell count was 3,700 cells/mm :~ with 48% neutrophils and band forms. Initial blood and CSF