Prophylactic Efficiency of 3-Weekly

Benzathine Penicillin G in Rheumatic Fever

Biilent Oran ~, Ayhan Ta~tekin ~, Sevim Karaaslan ~, Levent Ba~ 2, Ali Ay~i~ek ~, Ayhan ~eri ~, Ali Siit~ii 3
and lbrahim Erkul I

Department of ~Pediatrics, 2Animal Science and 3Microbiology, Selr University, %p Fakiiltesi ~ocuk
Klini~i, Konya, Turkey

Abstract. Benzathine penicillin G (BPG) is effective for secondary prophylaxis of rheumatic fever (RF). However, interval
between injections a remains a controversial matter. In a study population of 74 patients, following the initial diagnosis of
RF, 3-weekly BPG (1.2 million units) regimen was started. During the first three-week period, serum penicilhn
concentrations were examined on the 7th, 14th and 21st days and throat culture done for group-A b hemolytic
streptococcal (GABHS) infection. Ten patients (13.5%) at 21st day of injection had low serum penicillin concentration after
the first BPG. GABHS was isolated in 5 patients during this period. Although two of these 5 patients had symptoms of
respiratory tract infection, according to laboratory data, the other three were accepted as carriers. All 74 patients were then
followed-up for rheumatic recurrence (RR) during long-term period (6 to 60 months, mean 25 • 5 months). There was no
RR among regular (missing no more than one injection a year) group, We concluded that 3-weekly BPG regimen was
satisfactory for secondary prophylaxis in RF, even though serum penicillin level was inadequate during the third week in
some of the patients, [Indian J Pediatr 2000; 67 (3) : 163-167]

Key words : Rheumatic fever; Benzathine penicillin G; Secondary prophylaxis.

RF is one of the most common causes of
cardiovascular disease in children and remains a
major public health problem in many parts of the
world 1,2. Even in developed countries, after a
dramatic decline, there has been an increase in the
incidence of RF 3"7. But it is unclear whether the
resurgence of RF in developed countries wilt be
sustained or whether it is merely an aberration in the
continuing d o w n w a r d curve of the incidence of this
disease s.
The single most important method of control of
RHD at the present time is secondary prophylaxis
using BPG for non-allergic patients. In our country, 3-
weekly regimen has been used as prophylactic
scheme, according to recommendation of American
Heart Association (AHA) for countries where
incidence of RF has been particularly high 9. But there
are arguments regarding the interval between BPG
doses m-12.Furthermore, there are some reports which
advocate 2-weekly regimen, from countries where RF
is still prevalent ~3.~4.We have presented our results of
Reprint requests : B01ent Oran, Sel~uk 0niversitesi, Tip
Fak01tesi (~ocuk Klini~i, Konya-Turkey. Fax : 0.332. 3232641,
3232644
3-weekly regimen on children with RF and rheumatic
heart disease (RHD) in Konya (a city located in the
middle of Anatolia). The goals of this study were to
investigate serum penicillin levels after BPG injection,
to determine overall RR rate, and to assess the effect
of inadequate serum penicillin levels on RR rate in
long-term follow-up.
MATERIALS A N D METHODS
From 1990 to 1995, 74 patients with RF and RHD,
who were referred to the Pediatric Cardiology Unit
were included in the study after parental consent. Of
the 74 patients, 31(4t.9%) were females and 43
(58.1%) were males. Age range was 6 to 18 years
(mean age 12 years) and weight ranged from 17 to 76
kg (mean 41 kg).
All the patients were diagnosed according to the
Jones criteria~L RHD was diagnosed on the basis of
physical findings and confirmed by
echocardiography. At admission, throat culture,
erythrocyte sedimentation rate, C-reactive protein
and anti streptolysin O (ASO) titers were determined.
In addition to the anti-inflammatory agents, 1.2
million units of BPG (Penadur LA 1.2, Wyeth) were

Indian Journal of Pediatrics, 2000; 67 (3) : 163-167

 B Q l e n t O r a n et al

applied every three weeks, regardless of age or d a y s 7, 14 and 21 after the BPG administration, and
weight (the first injections were given by a nurse at thereafter, every 3 months. Patients were4 informed
our institution). Patients with penicillin allergy were about the manifestations of RF a n d upper respiratory
not included in the study. The patients were seen on tract infection a n d if a c o m p l a i n t suggestive :of
infection appeared they were asked to come back. O~
TABLE 1 : Clincial Features During the Initial Attacks
d a y s 7, 14 a n d 21 after the first infection, patient'.,
Findings Case number % were e x a m i n e d for u p p e r respiratory tract infectioa
and then for RR. In addition to throat culture, acute-
Arthritis and carditis 28 37.8 phase reactants, ASO titers, a n d penicillin levels were
Arthritis alone 23 31.1 d e t e r m i n e d on the same d a y s a n d thereafter, when
Carditis alone 10 13.5 d e e m e d necessary. No patient h a d renal or liver
Chorea alone 8 10.8 problem.
Chorea and carditis 3 4.1 "True streptococcal infection" is d e f i n e d as
Arthritis, chorea and carditis 1 1.35 positive throat culture a n d a serological response to
GABHS infection. "Streptococcal carrier" is also
Arthritis and chorea 1 1.35
d e f i n e d as h a v i n g positive throat culture and no
Total ~ 74 100.0 serologic response ~6. " R e c u r r e n c e " is defined as
reappearance of m a n i f e s t a t i o n s of RF, plus
TABLE 2 : Serum Penicillin Levels bacteriological a n d / o r i m m u n o l o g i c a l evidence of
recent streptococcal infection,in patients whose
Days Mean + SD max. rain. illness h a d been inactive for at lea.~t 2 m o n t h s after
(lag/ml) (pg/ml) (pg/ml) cessation of suppressive therapyC
7th 0.72 _+0.56 3.62 0.11 Patient compliance w i t h the p r o g r a m m e win.
14th* 0.36 +_0.15 0.78 <0.01 classifed into 3 ,ategories on the basis of the average
n u m b e r of injections missed yearly : (a) "regular" if
21st* 0.14 _+0.12 0.58 <0.01
no m o r e than one injection missed in a year; (b'}
*X2= 63.29; p = 0.000 "irregular" if 2 to 4 injections were missed in a year;

TABLE 3 : Correlation Between Streptococci Isolation and Penicillin Level

Patients with positive throat culture for GABttS

Day after infection case I case 2 case 3 case 4 case 5

Day 7 0.40 0.43

Day 14 0.73 <0.01
Day 21 0.22 0.20
Total 5 patients (serum penicillin concentrations ~g/ml)
a n d (c) " d r o p o u t " if m o r e t h a n 4 injections were
missed in a year.
Table 4 : Compliance with 3 - w e e k l y Regimen and the Re-
lationship with Rheumatic Recurrences Assay

Compliance Case No. of patients % GABHS was identified by m e a n s of bacitracin disc.

numbers with recurrence The concentration of penicillin in serum was assayed
by reversed-phase high performance liquid chroma-
Regular 62 0 0 t o g r a p h y (HPLC) (Liquid c h r o m a t o g r a p h y : LC-6A
Irregular 8 7 87.5 S c h i m a d z u , detector : UV-VIS-spectrophotomet-
Drop out 4 2* 50 ric)~.lL The lowest concentration of the d r u g detector
Total 74 9** 12.2 of this technique was 0.01 ~ g / m l .
Statistical analysis was d o n e by m e a n s of Chi-
*X2= 30, 59; p = 0.000; **X2= 21, 29; p = 0,000
Square and Fridman ANOVA by using the statistical
164 Indian Journal of Pediatrics, 2000; 67 (3)