Supplemental Digital Content TABLE 1. Studies Analyzed and Pertinent Characteristics
First Author
Year
Study
No.
Quality
Score*
Penicillin Description
Primary/
Second
Subject Age
Mean/Range (yr)
Health Status
Assay Method
Detection
Limit (μg/ml)
Stollerman2
Stollerman2
1952
1
2i
15
15
BPG a
BPG a
S
S
6-14
6-14, & 4 adults
RF pts
RF pts
M luteus cup plate diffusionr
M luteus cup plate diffusionr
0.0125
0.0125
Wyeth Lab6
1950s
3g
3
Benzathine penicillin
NA
NA
NA
NA
0.0125
Putnam34
1954
4
12
N-N'dibenzyl…b
S
28-53
Various pts
M luteus cup plate diffusionr
0.020
Ragab4
1954
5g
3
Benzathine penicillin
S
NA
NA
NA
0.009
12
BPG a
S
13-67
Pneumo pts
NA
Walker3
1954
6
White5
1955
Mazziconacci6
1957
8
Wright37
Wright37
Wright37
1959
1959
1959
Carron39
Carron39
15
BPG
P
Adult
Hlthy
M luteus disk plate
15
BPG
S
4-15
NA
S. aureus plate diffusion
0.009
9j,k
10 j,k
11 j,k
15
15
15
BPG
BPG
BPG
P
P
P
Adult
Adult
Adult
Hlthy prisoners
Hlthy prisoners
Hlthy prisoners
M luteus plate diffusion r
M luteus plate diffusion r
M luteus plate diffusion r
0.0125
0.0125
0.0125
1961
1961
12
13d,i
15
15
Benzathine penicillin c
Benzathine penicillin c
S
S
Children,
Children,
RF pts
RF pts
M luteus plate diffusion r
M luteus plate diffusionr
0.009
0.009
Raghuram35
Raghuram35
Raghuram35
Raghuram35
1979
1979
1979
1979
14
15
16
17
15
15
15
15
Benzathine penicillin
Benzathine penicillin
Benzathine penicillin
Benzathine penicillin
P
S
P
P
~22±2
~22±2
~22±2
~22±2
Hlthy
RF, RHD pts
Hlthy
Hlthy
M luteus plate diffusionrt
M luteus plate diffusion rt
M luteus plate diffusion rt
M luteus plate diffusionrt
0.020
0.020
0.020
0.020
Ginsburg29
1982
18
15
BPG
S
2-11,
Impetigo pts
M luteus plate diffusionr
0.008
Decourt28
1983
19
15
BPG ("Benzetacil")
P
20-25
Hlthy
M luteus plate diffusionr
0.005
diffusionr
0.002
Saran198540
Lue30
Saran198641
1985
1986
1986
7
0.02
diffusionr
h
20
21
o
22
12
Benzathine
15
BPG
12
Benzathine
penicillin d
penicillin d
S
Adult,
P
4-19
S
=10.5
=10.5
=5
=23
Child (12+/-1.7)
RHD pts
M luteus plate
RF pts
NA
RHD pts
M luteus plate
0.020
diffusion r
Padmavati33
1987
23
15
Benzathine penicillin
S
9-12
RHD pts
M luteus cup plate
Bégué25
1988
24
15
benzathine-benzylpenicillin
S
“Children”
RF pts
B. subtilis plate diffusion
diffusionr
Kaplan21
0.01
diffusionr
0.002
NA
NA
Kaplan21
1989
1989
25
26n
15
15
BPG
BPG
S
S
26-54
NA
RF pts
RF pts
M luteus plate
M luteus plate diffusionr
0.014
0.014
Thamlikitkul36
1992
27
15
BPG
S
29
Adult RF/RHD pts
M luteus plate diffusionr
0.015
Zaher38
Zaher38
1992
1992
28p
29p
15
15
BPG e
BPG e
S
S
8-16
8-16
RF pts
RF pts
S. aureus plate diffusion os
S. aureus plate diffusion os
0.022
0.022
Dorobat42
1992
30
15
Benzathine penicillinf
S
Adult
Various Ill
S. aureus plate diffusion o
0.03
Meira32
1993
1993
1993
31
32
33
15
15
15
BPG
BPG
BPG
S
S
S
“Adolescents”
“Children”
“Children”
RF pts
RF pts
RF pts
M luteus plate
M luteus plate diffusionr
M luteus plate diffusionr
0.006l
0.006l
0.006l
Daniels27
1994
34
15
BPG (“Bicillin”)
S
~13(±3)
RF pts
M luteus plate diffusionru
0.015
Meira32
Meira32
diffusionr
15
BPG (“Bicillin”)
S
29 (16-49)
RF pts
M luteus plate diffusionr
0.025
15
BPG
S
~10 (3-19)
RF pts
M luteus plate diffusionr
0.020
37
15
BPG ("Bicillin," Wyeth)
P
NA (~18-25)
Hlthy Army
M luteus plate diffusionr
0.006
2000
38q
15
BPGd
S
12 (6-18)
RF pts
HPLCv
0.010
2000
39
15
Benzathine penicillinc
P
16-60
Various ill & Hlthy
NA
0.012
Currie26
1994
Lue31
1994
36
Bass22
1996
Oran24
Belov43
35
o
Abbreviations: Hlthy, healthy; HPLC, high-performance liquid chromatography; MU, million units; NA, not available; RF, rheumatic fever; RHD, rheumatic heart disease
The articles are ordered by year published.
Studies that did not use 1.2 MU are not included in the analysis except for the Stollerman et al2 second study, which used 1.25 MU.
*The 5 categories of quality-assessment were: (1) description of the characteristics of the populations, (2) specification of number of subjects at each time point, (3) adequate
laboratory methods description, (4) results consistent with a reasonable range of published results, and (5) publication in a peer-reviewed journal. Each study was rated
dichotomously by each author on each of the five categories. Thus, each study had a total possible score of 0 to 15.
a
Benzathine penicillin G (N-N'dibenzylethylenediamine).
b
N-N'dibenzylethylenediamine.
c
Benzathine penicillin –“Extencilline.”
d
Benzathine penicllin (“Penadure LA-12,” Wyeth).
e
“local preparation” in Alexandria Egypt.
f
Benzathine penicllin (“Moldamin,” prepared in Romania).
g
The data reported here are taken from Mazziconacci et al.6 The original article or report is unavailable.
h
Different numbers of subjects were tested at different time points.
iThis study used two simultaneous 0.6MU injections rather than one 1.2MU.
j
Only the groups that were examined for serum pen G levels without prednisolone or procaine are included for this meta-analysis.
k
The first 2 groups were in a crossover design. For purposes of this meta-analysis, they will be treated simply as 2 groups receiving the same treatment in parallel
l
Levels were measured down to and reported as >0.01 μg/ml.
m
There were 2 groups, 1 receiving prophylaxis every 2 weeks and 1 every 3 weeks.
n
In Kaplan et al21, the 10 subjects in the first group are counted again in this aggregate of all measurements. The first group was identified with an age range, the second was not.
The meta-analysis takes this into account.
o
The data set from the Lue et al 199431 study was apparently included in the larger data set reported in the Lue et al 199614 study. It is assumed that the age mean and range and
dosage in the 1996 study are the same as reported in the 1994 study.
p
Kassem et al13 reported on the same data set as Zaher et al.38 The Zaher article is represented in this meta-analysis.
q
The Oran et al24 results for mean levels differed from the other studies by a factor of 10 and were excluded from the analysis of mean levels. However, the percentages above
minimum protective that they reported appear within the expected range and were included in that analysis.
r
The organism is called “Sarcina lutea” or “Sarcina luteus” in the article.
s
See Grove and Randall46 for the method.
t
See Lightbrown and Sulitzeanu47 for the method.
u
See Sutherland and Rolindson48 for the method.
v
High-performance liquid chromatography (HPLC-6A Schimadzu detector, UV-VIS-spectrophotometric).
References, Supplemental
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2
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3
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