Benzathine Penicillin for Unilateral Lobar or Segmental
Infiltrates Presumptively Caused by Streptococcus
Pneumoniae in Children 2-12 Years Old
by Paulo Augusto Moreira Camargos,* MD, ScD, Mark Drew Crosland Guimaraes,** MD, ScD, and Cid Sergio
Ferreira,*** MD, ScD
Departments of ^Pediatrics, "Preventive and Social Medicine, and ***Radiology, School of Medicine, Federal
University of Minos Gerais, Av. Alfredo Balena 190, 30130, Belo Horizonte, Brazil
Summary
A randomized controlled study was carried ont to assess the efficacy of a single dose of benzathine
penicillin for treating children 2-12 years old with presumed 5. pneumoniae pneumonia. Onehundred-and-seventy-six children screened at self-referral pedlatrk emergency services in Belo
Horizonte, Brazil, were randomized to only one injection of benzathine penicillin (n = 93, casegroup) or a 7-day procaine penicillin regimen (n = 83, control-group), upon diagnosis of
pneumococcal pneumonia based on clinical and radiological characteristics. Follow-up was carried
out on the second day after treatment and around the 7th and/or 14th day after treatment allocation.
No statistical significant difference was found for sociodemographic, clinical, laboratory or
radlographlc characteristics among the two groups. Evident or total radiographic clearing was
demonstrated for 92 J and 95.1 per cent of the benzathine penicillin and procaine penicillin groups,
respectively (P = 0.54). Benzathine penicillin may be considered an alternative to classic regimens
for treating pneumonia due to sensitive strains of S. pneumoniae among children 2-12 years old.
Other benefits are its lower cost, better compliance and low rates of adverse reactions.
Introduction
About 13 million children less than 5 years of age die
every year in the world, 95 per cent of them in
developing countries. Pneumonia is one of the leading
causes, accounting for about four million of these
deaths.1 Furthermore, mortality rates among this age
group are 30-70 times higher than in industrialized
nations, most likely due to unfavourable environmental
and socio-economic conditions in addition to scarce
resources and poor organization of health services.2*3 In
1985, just before the beginning of the present study, the
Acknowledgments
The authors wish to thank the staff of the "Laborat<5rio de
Pesquisas em Bacteriologia' and the pediatric, nursing staff and
directors of the 'SUCC-Santa Casa', 'Centra Geral de
Pediatria', 'Hospital Sarah Kubitschek' and 'Hospital das
Ch'nicas da Universidade Federal de Minas Gerais'. We also
thank Dr David Vlahov, from the Department of Epidemiology,
Johns Hopkins School of Hygiene and Public Health, for
reviewing the manuscript.
This study was supported by a grant from Ministry of Science
and Technology/FINEP-Financiadora Nacional de Estudos e
Projetos-, Brazil, Grant nr. 4.1.85.0752.00.
Correspondence: Mark D. Guimaraes, MD, ScD, Departmento
de Medicina Preventativa e Social, Faculdade de Medicina,
UFMG, Av. Alfredo Balena 190, 10 Andar, 30130-100, Belo
Horizonte, MG, Brazil.
Journal of Tropical Pediatrics
Vol. 43
December 1997
age-specific mortality rate (0-5 years old) in Belo
Horizonte, Brazil, had reached 1.1/1000.3
The main etiologic agents of bacterial pneumonia
among children in developing countries are Streptococcus pneumoniae, the most frequently isolated microorganism in some countries, including Brazil, and
Haemophilus influenzae.1'**6.
The World Health Organization has emphasized the
relevant role of antimicrobial treatment in reducing mortality rates, usually directed toward the most common
aetiological agents using drugs with advantageous costbenefit and cost-effectiveness ratios.
However, definitive diagnosis of pneumonia, i.e.
isolation of the causative pathogen, is difficult. The
existing tools for specific diagnosis present low sensitivity and/or poor specificity. The invasive nature of
some of these procedures and the high cost are additional
barriers for use in routine clinical practice. Thus, it is
well known and widely acceptable that diagnosis of
pneumonia depends upon the clinical suspicion of a
particular pathogen and it is usually correlated with the
age group, clinical history, physical examination and
radiologic settings.'17 Currently, therapy is often initiated
on a presumptive basis due to these difficulties in
identifying specific etiologic agent in every patient,
requiring empiric treatment, especially in the developing
world.1-7
Another useful information for making presumptive
© Oxford University Press 1997
353
P. A. M. CAMARGOS ET AL
etiologic diagnosis concerns the source of infection, i.e.
whether community-acquired or hospital-associated
pneumonia. 5. pneumoniae and H. influenza* are
commonly community acquired.
Standard treatments for pneumonia caused by S.
pneumoniae include, among others, 7-day procaine
penicillin. This implies an increased cost and possible
low compliance at the primary health care level in
developing countries. However, some case studies have
shown the efficacy of one dose of benzathine penicillin
for lobar and segmental pneumonia presumed to be due
to this micro-organism.8"10
To date, no known controlled clinical trial has been
conducted for assessing the role of benzathine penicillin
for treating pneumococcal pneumonia. In view of the
epidemiologic relevance of pneumonia among children
in Brazil and in other developing countries, and the
lower cost, easier compliance and minor rates of side
effects of only one injection of benzathine penicillin, the
present investigation was carried out in order to verify its
efficacy in presumed lobar and segmental 5. pneumoniae
pneumonia as compared to procaine penicillin.
Materials and Methods
The efficacy of benzathine penicillin G (case-group) for
treating presumed pneumococcal pneumonia among
children 2-12 years old was assessed through a randomized clinical trial carried out in Belo Horizonte,
Brazil, between June 1986 and September 1991,
by comparison with a standard seven-day procaine
penicillin G regimen (control-group).
Children aged 2-12 years old with suspected lobar or
segmental pneumonia were first screened at two major
pediatric emergency services. These are self-referral
public health services, which cater for mostly the lower
socio-economic segments of the population. These
patients were then referred to the research protocol for
clinical and radiologic re-evaluation, carried out at the
University Hospital at the Federal University of Minas
Gerais, Belo Horizonte, Brazil.
Inclusion and exclusion criteria
The following criteria were defined for admission into
the protocol: (a) community-acquired pneumonia; (b)
children aged 2-12 years old; (c) fever, measured by
axillar temperature as s38°C, and/or use of antipyretic
drugs for the current condition; (d) symptoms and
physical signs of acute bacterial pneumonia; (e) chest
roentgenogram on frontal and lateral projections at
admission, showing homogenous and well defined lobar
or segmental alveolar (air space) consolidation,
restricted to one lobe; (f) no other X-ray abnormality
in the ipsi or contralateral lung; and (g) no antibiotic use
for the current condition.
Patients with the following conditions were excluded:
(a) severe cases, such as children presenting central
cyanosis and requiring oxygen therapy; (b) direct and
indirect signs of atelectasis; (c) post-measles pneumonia;
354
(d) sickle-cell anaemia; (e) cardiopathy; (f) immunodeficiencies; (g) previous splenectomy; (h) previous
allergic reaction to penicillin; and (i) history of
hospitalization within 2 weeks prior to admission.
Treatment regimens
After admission into the protocol, children were
randomized to the benzathine or the procaine group
according to a predesigned schedule. Children weighing
20 kg or less received one single dose of 600,000 units of
benzathine penicillin G and those weighing more than
20 kg, one single dose of 1,200,000 units. The comparison group received 300,000 units of procaine penicillin
G given by intramuscular route, every 24 h for those
weighing 20 kg or less, and every 12 h for those weighing
more than 20 kg, over a period of 7 days.
Randomization was carried out by a trained staff
member, blind to treatment or control groups, using four
identifying letters, randomly selected for benzathine (W,
Z) and procaine (X, Y), enclosed in sealed envelopes,
and referred to a different staff member for administering the drug. This procedure was necessary due to the
difficulty in masking treatments (one dose for benzathine
and seven or 14 doses for procaine).
The single benzathine penicillin dose or the first
procaine penicillin dose was administered upon diagnosis at the same University Hospital. Patients were
given especial prescription forms, along with the vials,
for the subsequent doses of procaine penicillin G to be
administered at public outpatient care units. They were
requested to bring the forms signed by a health attendant
or physician, confirming date and time of injections.
Laboratory tests
In addition to blood cultures (performed according to
standard procedures up to the ninetieth patient),
erythrocyte sedimentation rate, C-reactive protein, and
white blood cell (WBC) count were carried out to
provide information on the bacterial origin of pneumonia
among the studied patients.
Follow-up and endpoint
Follow-up visits were scheduled for the second (clinical
control), the seventh (clinical and radiologic control) and
fourteenth (clinical and radiologic control) days at the
same hospital. Clinical evaluation was performed by a
member of the research team, who happened to be on call
at the moment of the scheduled control, and not
necessarily by the physician who initially examined the
patient or the X-ray at admission.
The endpoint considered was defined as radiological
improvement measured by evident and progressive
reduction or disappearance of lobar/segmental consolidations, verified at each follow-up point. The radiological assessments were carried out in a blind and
independent fashion by only one radiologist
Questionnaires and protocol
A standard protocol was designed to collect information
Journal of Tropical Pediatrics
Vol. 43
December 1997
P. A. M. CAMARGOS ET AL
on clinical history, radiologic findings, laboratory tests
result and sociodemographic characteristics. Forms were
tested and coded for data entry and analysis.
Statistical aspects
The initial sample size estimate was 150 patients in each
group and was based on a type 1 error (or) of 0.05 and a
type II error (/?) of 0.20, aiming at detecting a 5 per cent
difference between the estimated efficacy of the standard
treatment (procaine penicillin) (100 per cent) and the
study regimen (benzathine penicillin). However, recruitment took longer than expected facing financial and
operational problems, such as several health service
strikes, resulting in reduction of the effective sample size
to 93 children in the benzathine group and 83 children in
the procaine group.
The statistical analysis included chi-square test and
Fisher's Exact test for the differences in proportion for
the dichotomous variables and 95 per cent confidence
limits for point estimates. The significance level
considered was 0.05.
Ethical aspects
The study protocol was reviewed and approved by two
independent Ethical Committee Boards, from the
Medical School of the Federal University of Minas
Gerais and the Ministry of Science and Technology.
Risks and benefits were explained to parents or legal
guardians of the children, and only those who voluntarily
agreed to participate were included in the study. All
information was confidential and only aggregate data are
presented.
If any patient did not respond to either treatment,
the chest film was repeated and the child reevaluated
and hospitalized. Depending on the clinical and
radiologic settings, therapeutic regimen was changed
and antibiotics recommended for H. influenzae or S.
aureus pneumonia, e.g. amoxicillin or ampicillin alone
or ampicillin in association with oxacillin, were
administered.
Results
One-hundred-eighty-one patients were initially screened
for participating in the study, but five were excluded
from analysis due to incorrect inclusion into the protocol,
leaving 176 patients for the final analysis (53 per cent in
the benzathine group and 47 per cent in the procaine
group).
Table 1 presents sociodemographic characteristics of
the studied population. Most of the participants in both
TABLE 1
Selected sociodemographic characteristics among benzathine and procaine groups
Benzathine group
(" = 93)
n (%)
Procaine group
(n = 83)
n (%)
69 (74.2)
15(16.1)
9 (9.7)
64 (77.1)
14 (16.9)
5 (6.0)
0.84
70 (75.3)
23 (24.7)
67 (80.7)
16(19.3)
0.49
66 (79.5)
15(18.1)
2 (2.4)
0.88
unknown
72 (77.4)
16(17.2)
5 (5.4)
Number of household members:
<10
£10
unknown
82 (88.2)
7 (7.5)
4 (4.3)
78 (94.0)
5 (6.0)
—
O.76t
Sex:
males
females
56 (60.2)
37 (39.8)
47 (56.6)
36 (43.4)
0.74
Age group:
2-6 years old
7-12 years old
58 (62.4)
35 (39.8)
42 (50.6)
41 (49.4)
0.15
Variable
1. Family monthly income*:
< 3 minimum wage
a 3 minimum wage
unknown
2. Head of household education:
literate
illiterate
3.
Number of household rooms:
<5
a5
4.
5.
6.
P-value
• 1 minimum wage = US$ 65.00.
t Fisher's Exact Test.
Journal of Tropical Pediatrics
Vol.43
December 1997
355
P. A. M- CAMARGOS ET AL
groups earned less than 3-monthly minimum wage, their
heads of households were literate, and they lived in
homes with less than five rooms. Although higher
proportion of children in the benzathine group were
males (60 per cent) and in the 2-6-year-old age group
(62 per cent), as compared to procaine group (57 and 51
per cent, respectively), these differences were not
statistically significant.
Clinical and radiologic characteristics were similar in
both groups (Table 2). Clinical presentation of most
children was abrupt (65 and 72 per cent for benzathine
and procaine groups, respectively), with fever and
evident signs of prostration. Radiological features
showed that 70 per cent of the benzathine group had
the right lung affected and 81 per cent showed evidence
of segmental consolidation, while in the procaine group
these were 81 and 77 per cent, respectively. No
statistically significant difference was observed for all
variables, showing reasonable comparability between
the two groups.
Most of the patients (79 and 83 per cent among
benzathine and procaine groups, respectively) had at
least one laboratory test (erythrocyte sedimentation rate
or WBC count or positive C-reactive protein) indicative
of bacterial pneumonia performed and found to be
positive. Among those patients with blood culture (53
per cent in benzathine group and 49 per cent in procaine
group), S. pneumoniae was isolated in 4 and 2 per cent,
respectively. It is important to note that no other bacteria
etiologically associated with lobar or segmental pattern,
such as H. influenzae or S. aureus, were isolated in the 84
remaining blood cultures.
TABLE 2
Clinical, laboratory and radiographic characteristics of benzathine and procaine groups
Benzathine group
(n = 93)
n (%)
Procaine group
(n = 83)
n (%)
Mode of presentation:
abrupt
insidious
unknown
60(64.5)
32 (34.4)
1(1.1)
59 (72.0)
22 (26.5)
2 (2.5)
0.36
Fever (2: 38°C):
present
absent
91 (97.8)
2 (2.2)
82 (99.0)
1 (1.0)
1.0*
93 (100.0)
83(100.0)
NA
87 (93.5)
6(6.5)
78 (94.0)
5 (6.0)
1.0*
65 (69.9)
28 (30.1)
67 (80.7)
16(19.3)
0.13
75 (80.7)
18(193)
64(77.1)
19 (22.9)
0.69
Laboratory exams}:
positive
negative
not-performed
73 (78.5)
0(-)
20(21.5)
69(83.1)
0(—)
14(16.9)
0.73
Blood culture t
positive
negative
not-performed
4(4.3)
45 (48.4)
44 (47.3)
2 (2.4)
39 (47.0)
42 (50.6)
0.68*
Variable
1.
2.
3.
4.
S.
6.
7.
Prostration:
present
absent
Use of antipyretics:
yes
no
Radiological findings:
(a) Localization
Right lung
Left lung
(b) Type of consolidation
Segmental
Lobar
f-value
• Fisher's Exact Test
NA = not applicable.
t Other laboratory exams positive = erythrocyte sedimentation rate & 20 mm/h and/or while blood cell
count a 15,000 per mm2 and/or presence of C-reactive protein.
t Blood culture positive = S. pneumoniae isolated, blood culture negative = any pathogen isolated.
356
Journal of Tropical Pediatrics
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P. A. M- CAMARGOS ET AL
TABLE 3
Hyperpyrexia clinical course among benzathine and procaine groups
Benzathine group
n (%)
Hyperpyrexia status
Fever
Fever
Fever
Fever
Total
relapsed within 24 h
relapsed between 24 and 48 h
was persistent at 48 h
was not recorded
Procaine group
(%)
71
70 (75.3)
8 (8.6)
10(10.7)
5 (5.4)
93 (100.0)
55
14
10
4
83
(66.3)
(16.9)
(12.0)
(4.8)
(100.0)
X 2 = 2 . 9 5 , P = 0.22 (NS).
TABLE 4
Completed visits according to scheduled follow-up
Benzathine group
Procaine group
Days of completed visits
7th and 14th days
7th day only
14th day only
Lost of follow-up
79
8
4
2
(85.0)
(8.6)
(4.3)
(2.1)
Total
93 (100.0)
68 (82.0)
10(12.0)
4 (4.8)
1(1.2)
83 (100.0)
2
X = 0.57, P = 0.74 (NS).
follow-up (around the 7th and 14th day) was satisfactory
for 85 and 82 per cent of the patients in the treatment and
control groups, respectively. Partial follow-up (around
the 7th or 14th day only) was accomplished for
approximately 15 per cent of the participants, while
only two patients (2 per cent) in the benzathine group
and one (1 per cent) in the procaine group were
considered lost to follow-up.
The therapeutic response was initially assessed
according to the initial randomization procedure, but
excluding those lost to follow-up (Table 5). Eighty-four
(92 per cent) and seventy-eight (95 per cent) of
the patients in the benzathine and procaine groups.
After administering the specified treatments, fever
declined in most children in the benzathine and procaine
groups (Table 3). Fever relapsed similarly in both groups
within 48 h (84 and 83 per cent for benzathine and
procaine groups, respectively), most of them occurring
within the first 24 h (75 and 66 per cent, respectively).
Fever was still persistent after 48 h for 11 and 12 per cent
of the patients in each group, respectively. Approximately, 5 per cent of the patients did not have
temperature properly recorded in the protocol, but this
was not statistically different between benzathine and
procaine groups (P = 0.22).
Table 4 shows that complete clinical and radiologic
TABLE 5
Therapeutic response according to X-ray films taken around the 7th and/or 14th days*
Procaine group
Benzathine group
n(%)
Response category
84 (92.3)
Evident or total
radiographic clearing
95% Q
(84.3-97.3)
"(%)
78(95.1)
Therapeutic failure
7 (7.7)
4 (4.9)
Total
91 (100.0)
82 (100.0)
95% a
(87.1-99.1)
P (two tail. Fisher's Exact Test) = 0.54 (NS).
Difference = 2.8 per cent, 95 per cent Cl, - 4 . 0 per cent to 10.0 per cent
Two patients in case-group and one patient in the comparison-group were lost of the follow-up and were not included
in this analysis.
Journal of Tropical Pediatrics
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December 1997
357
P. A M. CAMAROOS ET AL
respectively, showed evident or total radiologic
clearing. The six bacteremic children improved
completely. Fisher's Exact test did not reveal any
statistically significant difference in the radiologic
response between the two treatments (P = 0.54,
difference = 2.8 per cent, 95 per cent confidence
interval for the difference =—4.0-10.0 per cent).
The lower limit for the point estimate of therapeutic
success for those receiving benzathine penicillin was 84
per cent
No adverse reaction to penicillin was verified in both
groups. Among the eleven patients who did not respond
to benzathine or to procaine penicillin G, five improved
with amoxicillin alone, three required ampicillin and the
remainder three children improved with an association of
ampicillin and oxacillin. It was not possible to confirm
the aetiological agent in these cases.
Choice of procaine penicillin as control group
The choice of procaine penicillin G as comparison
therapy was based on its wide acceptance in the
management of pneumococcal pneumonia and its
similarity of antimicrobial spectrum with benzathine
formulation, in particular against pneumococci highly
sensitive to penicillin G. In addition, it is well known
that both preparations of penicillin are not the first
line drugs against other micro-organisms that can
eventually determine lobar or segmental consolidations
in the studied age group. For example, in addition
to S. aureus, the procaine formulation should not be
used alone if//, influenzae is a likely pathogen, although
this drug can be efficacious in some patients.
Other antibiotics and chemotherapeutic agents such as
penicillin V, clavulanic acid/amoxicillin, chloramphenicol and co-trimoxazole were not considered also in view
of either a higher cost and/or lower compliance. Furthermore, the use of some of these drugs in the controlgroup could have biased the results due to their good
efficacy against H. influenzae and S. aureus, pathogens
also responsible for a lobar or segmental radiographic
pattern.
Discussion
Eligibility criteria
Difficulties for identifying the specific aetiological agent
of pneumonia among children, commonly reported in the
medical literature, were also present in this study.
Definitive diagnosis, based on isolation of the microorganism in blood culture, was used in the first 90
subjects, when it was interrupted due to its low
sensitivity obtained (6.7 per cent of positive cultures),
its high cost and operational constraints.
This way, the diagnostic criteria of presumed pneumococcal pneumonia were based on epidemiological,
clinical and radiologic characteristics, which are
commonly used in routine clinical practice. Reasons
for the criteria used include: (a) S. pneumoniae and
H. influenzae are more frequently associated with
community-acquired pneumonia;1-4^ (b) pneumococcus
is the most frequent agent of bacterial pneumonia among
children 2-12 years old; 17 (c) chest roentgenogram
on frontal and lateral projections at admission,
showing homogeneous and well defined lobar or
segmental alveolar (air space) consolidation, restricted
to one lobe, represent a pattern commonly associated
with pneumococcal pneumonia;7'""18 and (d) no other
X-ray abnormality in the ipsi or contralateral lung was
considered important to exclude pneumonia due to other
microorganisms, such as S. aureus.
In order to avoid cases due to other micro-organisms
and to exclude clinical conditions potentially related
with poor prognosis, the following exclusion criteria
were defined: (a) direct and indirect signs of atelectasis,
aiming at excluding cases due to viruses or Mycoplasma
pneumoniae; (b) history of hospitalization within 2
weeks prior to admission mainly to avoid cases due
to 5. aureus; (c) severe cases; (d) post-measles pneumonia; (e) sickle-cell anaemia; (f) cardiopathy; (g)
immunodeficiencies; (h) previous splenectomy. Patients
with previous allergic reaction to penicillin were also
excluded.
Therapeutic response evaluation
Although other authors have evaluated several simplified
regimens of penicillin G among children, adolescents
358
Journal of Tropical Pediatrics
Diagnosis of Streptococcus pneumoniae pneumonia
Besides fever, prostration and the sudden onset of the
clinical picture (comprising the respiratory system
examination findings), one of the main characteristics
of pneumococcal pneumonia is a rapid improvement of
the clinical abnormalities (e.g. tachypnoea, dyspnoea)
and a quick resolution of fever following appropriate
therapy.719-20 Although precise aetiological diagnosis
was performed in only few subjects, this latter clinical
finding was present among 83 per cent of the participant
children (Table 3) and is supporting evidence that they
indeed had pneumococcal pneumonia.
Laboratory data are consistent with these clinical
characteristics. In fact, although only six patients had
definite diagnosis of pneumonia due to S. pneumoniae, a
higher proportion (approximately 80 per cent) among
the two groups showed abnormalities in erythrocyte
sedimentation rate or C-reactive protein or WBC count
that suggest bacterial infection.
Radiological features of lobar or segmental presentations are also strong indicators of pneumococcal pneumonia in this age group, as previously mentioned. 7 "-' 8 .
In addition, the predominance of segmental presentations, as compared to lobar, is in agreement with Kuhn's
statement that pneumococcal pneumonia rarely affects
an entire lobe.13
Thus, it can be concluded that, even lacking certainty
of aetiological diagnosis of pneumonia, all children
presented clinical, laboratory, and radiological characteristics that are strongly suggestive of pneumococcal
pneumonia.
Vol. 43
December 1997
P. A. M. CAMAROOS ET AL
and/or adults,21"27 our literature search did not identify
any randomized controlled study with similar sample
size that has evaluated benzathine penicillin in presumed
or proven pneumococcal pneumonia among children.
In addition, standard pediatrics textbooks, comprising
respiratory tract and infectious diseases reference books,
do not include benzathine penicillin as therapeutic
recommendation in the management of pneumococcal
pneumonia.
Most published papers referring to the use of this drug
have been from Brazil.8"10 The diagnostic criteria were
generally based on clinical and radiological (only lobar
presentation) characteristics with therapeutic success
rates varying from 86 to 100 per cent.24-26.
In fact, such results agree with many correlated
evidences. Interim data reports from a recent International Collaborative Study have shown that, in Brazil,
the proportion of 5. pneumoniae strains sensitive to
penicillin was 85-90 per cent. Of these 58 per cent
were pneumonia cases and 48 per cent were meningitis
cases.28-29
In addition, the evaluation of rheumatic fever prevention schedules may offer valuable pharmacological
information. It has been shown that one dose of
1,200,000 units of benzathine penicillin maintains
bactericidal serum concentrations (> 0.03 unit/ml) for
group A (3-haemolytic streptococci for a minimum of 7
days in the majority of the patients.30'31 It is reasonable
to admit that such serum levels may also be bactericidal
for highly sensitive strains of S. pneumoniae. Penicillin
has good diffusion rates into lung tissues and serum
concentration is considered a valid estimate of the lung
tissue concentration.
Another pharmacological comment has been provided
by Klein, who pointed out that intramuscular benzathine
penicillin is appropriate only for highly sensitive
organisms in tissues that are well vascularized so that
the drug can diffuse readily to the site of infection.32 This
assumption may apply to the lungs given that the
pulmonary capillary bed is the largest vascular bed in the
body and covers a surface area of 70-80 m2.33
As an empiric statement. Smith points out that '...the
pneumococcus is, in fact, so sensitive to penicillin that
the optimum dosage schedule is difficult to determine.
The effective dose is probably much smaller than that
ordinarily used; moreover, the interval between injections may be much longer'.34 This statement, which
evidently does not apply to resistant pneumococci, agrees
with a World Health Organization memorandum, i.e. 'a
single intramuscular dose of benzathine penicillin is
adequate in selected cases in many areas'.35
On the other hand, the proportion of therapeutic
failure verified here (8 and 5 per cent, for, respectively,
benzathine and procaine groups) is predictable, even
without bacteriological confirmation. This proportion
can be explained by the likely involvement of other
ctiologic agents also responsible for lobar or segmental
shadows against which benzathine or procaine penicillin
arc not effective such as, pneumococci with intermediate
Journal of Tropical Pediatrics
Vol.43
December 1997
or high level resistance to penicillin G, Haemophilus
influenzae, staphylococci or Mycoplasma pneumoniae.
In this sense, the randomization process would theoretically balance distribution of these micro-organisms in
the two groups, i.e. 8 and 5 per cent, in cases and
controls, respectively.
Conclusive remarks
The results herein presented suggest that benzathine
penicillin G in one single dose may be considered a
reasonable alternative to 7-day regimen of procaine
penicillin in the management of pneumococcal pneumonia, mainly among mild to moderate cases, the most
frequent ones in children older than 2 years old.
However, it should be emphasized that this protocol is
not applicable to countries where resistant pneumococci
are prevalent.
Furthermore, consideration should be given to other
benefits such as very low cost, optimal compliance, and
low rates of adverse reactions. As an example, the price
of one injection of 600,000 units of benzathine
penicillin, in 1981, was US$ 0.20, at least three times
less than a treatment course of procaine penicillin lasting
5 days.35 The virtual 100 per cent compliance can be
easily achieved since health workers can administer one
single dose of the drug immediately after the diagnosis,
at a health centre or at home.
Moreover, according to the results presented in
Table 3, the possibility of non-response to benzathine
penicillin could be detected by physicians, health agents,
or even by the parents, either because of persistence of
fever after 24-48 h of drug administration or because
of evident clinical and/or radiological deterioration.
These changes should be immediately followed by an
individualized therapeutical reassessment.
The authors understand that this set of benefits has
considerable clinical relevance, especially considering
the high morbidity and mortality rates caused by
pneumococcal pneumonia in developing countries. It
also contributes to compensate the reduced statistical
power due to incomplete ascertainment.
Finally, it should be desirable that other randomized
controlled studies, comprising larger sample size with
definite bacteriological diagnosis, were conducted under
various epidemiological conditions to assess benzathine
penicillin G efficacy in the treatment of pneumococcal
pneumonia. Ideally, these clinical studies should be
preceded by in vitro surveys to assess the local and/
or regional prevalence of pneumococci sensitive to
penicillin.
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Journal of Tropical Pediatrics
Vol.43
December 1997