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Journal of Clinical Microbiology, August 1999, p. 2743-2744, Vol. 37, No. 8
0095-1137/99/$04.00+0
LETTERS TO THE EDITOR
Determination of Penicillin Resistance in Streptococcus
pneumoniae and Use of Co-Trimoxazole in Treatment of Pneumococcal
Pneumonia
 |
LETTER |
We read with interest the article by Saha et al. (6) on
antimicrobial resistance and serotype distribution of
Streptococcus pneumoniae. We would like to highlight certain
aspects in the article which need to be looked at. The authors state
that the E test was performed to determine the MICs for all the
S. pneumoniae strains isolated as part of the study. For
penicillin, the oxacillin screen, which is an acceptable procedure
(5), was used. The strains resistant to oxacillin by disc
diffusion were subsequently found to be intermediately resistant or
completely resistant to penicillin by the E test.
The E test is only a commercial method, not a "gold standard," for
MIC determination. The E test has the accuracy to agree within 1 doubling dilution of the reference penicillin MIC for 90% of strains
and within 2 doubling dilutions for 99% of the strains (3).
Even though a good correlation between the reference MIC by agar
dilution methods and the E test MIC has been observed (4), a
tendency for the penicillin MIC to be slightly lower by the E test than
by reference agar dilution method has been observed (3).
There have been reports that strains resistant to penicillin by
reference MIC dilution methods were found to be intermediately
resistant by E test (1). The authors do not state that
internal quality control procedures such as testing of reference
strains, blinded determination by independent observers, and checking
for internal reproducibility of the E test results were used. A few
strains resistant to penicillin by the E test could have been sent to a
reference laboratory for confirmation of values.
The second issue involves co-trimoxazole resistance. The study reports
an overall resistance to co-trimoxazole of 64.1%. It would have been
interesting to compare the resistance to co-trimoxazole of the strains
of S. pneumoniae isolated from invasive sites with that of
strains from noninvasive sites. The authors should have looked at
strains from patients with proven pneumococcal pneumonia since they
have discussed the use of co-trimoxazole in treatment of pneumonia.
This would have been critical to support their argument that
co-trimoxazole may not be useful for the treatment of pneumonia. At our
center, a resistance level of 47.8% was found in the IBIS study
(2) in cases of bacterial pneumonia confirmed by a positive blood culture across all age groups. Interestingly, the level of
resistance was found to differ across the age groups studied, with
levels of resistance lower, at 16%, in the below-2-year age group than
in the adult age group.
In a nasopharyngeal colonization study at our immunization clinic where
children below 1 year of age were enrolled, the percentage of
co-trimoxazole resistance was only 5.4% (3a). However, the percentage of resistance was significantly higher, at around 64%, in
children between 2 and 5 years of age (4a) in a
community-based nasopharyngeal colonization study. This difference in
levels of resistance with respect to invasive versus noninvasive and
hospital versus community settings in children under the age of 5 is
notable as this may have implications for antibiotic treatment in that age group, particularly in developing countries. This aspect may be
interesting to follow up and study in detail since it may have a direct
impact on the formulation of an appropriate antibiotic policy.
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FOOTNOTES |
*
Phone: 91-416-222102 ext. 2033
Fax: 91-416-232103/232035
E-mail: mkl{at}micro.cmc.ernet.in.
| |
REFERENCES |
| 1.
|
Brown, D. F. J.
1992.
Summation.
Diagn. Microbiol. Infect. Dis.
15:489-492.
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| 2.
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Invasive Bacterial Infection Surveillance (IBIS) Group and International Clinical Epidemiology Network (INCLEN).
1999.
Prospective multicentre hospital surveillance of Streptococcus pneumoniae disease in India.
Lancet
353:1216-1221[Medline].
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| 3.
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Jacobs, M. R.,
S. Bajaksouzian,
P. C. Appelbaum, and A. Bolstrom.
1992.
Evaluation of E test for susceptibility testing of pneumococci.
Diagn. Microbiol. Infect. Dis.
15:473-478[Medline].
|
| 3a.
| Jebaraj, R., T. Cherian, P. Raghupathy, K. N. Bramadathan,
M. K. Lalitha, K. Thomas, and M. C. Steinhoff. Nasopharyngeal
colonisation of infants in southern India with Streptococcus
pneumoniae. Epidemiol. Infect., in press.
|
| 4.
|
Lalitha, M. K.,
D. J. Manayani,
L. Priya,
M. V. Jesudason,
K. Thomas, and M. C. Steinhoff.
1997.
E test as an alternative to conventional MIC determination for surveillance of drug resistant S. pneumoniae.
Indian J. Med. Res.
106:500-503[Medline].
|
| 4a.
| Lalitha, M. K. Unpublished data.
|
| 5.
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National Committee for Clinical Laboratory Standards.
1994.
Performance standards for antimicrobial susceptibility testing: fifth international supplement, vol. 14, no. 16. NCCLS document M100-S5.
National Committee for Clinical Laboratory Standards, Villanova, Pa.
|
| 6.
|
Saha, S. K.,
N. Rickitomi,
M. Ruhulamin,
H. Masaki,
M. Hanif,
M. Islam,
K. Watanabe,
K. Matsumoto,
R. B. Sack, and T. Nagatake.
1999.
Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae strains causing childhood infections in Bangladesh, 1993 to 1997.
J. Clin. Microbiol.
37:798-800[Abstract/Free Full Text].
|
| | | | |
M. K. Lalitha*
Anand Manoharan
Rekha Pai
Department of Clinical Microbiology
Christian Medical College & Hospital
Vellore 632004, Tamilnadu, India
|
| | | | |
Kurien Thomas
Department of Medicine Unit II
Christian Medical College & Hospital
Vellore 632004, Tamilnadu, India
|
| |
AUTHORS' REPLY |
We thank Dr. Lalitha and colleagues for their interest in our paper
(5) and appreciate their concern about the E test; this
letter will allow us to show some additional analysis of our results.
We do agree that the E test is a commercial method like any of the
other commercially available microdilution systems. We are aware of the
tendency of the E test to show a slightly lower (a log2
dilution, 90% agreement) MIC (1-3). The E test uses a
continuous-gradient scale, whereas the broth or agar dilution method
uses doubling dilutions. Any strain for which the MIC is 2.0 µg/ml by
the dilution method is anywhere within the range of 1.01 to 2.0 µg/ml
as there is nothing in between. On the other hand, the E-test strip may
be more precise as it contains the concentrations in between the
doubling dilutions (1). Anyway, resolution of this debate
needs some experimental work with fractional dilutions. In spite of
this minor discrepancy between the E-test and dilution methods, the E
test has possibly been the most widely used method since its
introduction and all groups recommended it as a potential alternative
to the conventional dilution method (1, 2). Going further in
their recommendations, Lalitha et al. (3) reported this test
to be simple, easy to interpret, cost-effective (it is rather
expensive), and reliable. They have also mentioned, as a noteworthy
point, that no errors either of false susceptibility or false
resistance were observed. Our aim is the economization of its use on
the basis of oxacillin disc screening so that routine laboratories in
developing countries can use it as a quick and simple way to detect
penicillin-resistant strains for the patients' benefit.
Despite these points mentioned above, we were cautious in interpreting
our results and making comments and did the fragmented analysis of MICs
for our S. pneumoniae strains to understand the consequence
of lower MICs (1 log2 dilution) by the E test. The analysis
showed that 12% (44 of 362) of our strains were within the MIC of
0.064 to 0.098 µg/ml; some (10%) of these strains may be classified
as relatively resistant if tested by broth or agar dilution. Even if
this is true, our study has identified four (1.1%) strains as
sensitive which could be classified as relatively resistant by the
dilution method. Similarly, we have 0.6% (2 of 362) of strains for
which MICs are 1.0 to 1.5 µg/ml, which are supposed to remain the
same, with possible variation in 10% of cases, by the dilution method.
If we ignore the fact of the continuous gradient of the E test and
consider that apparent difference of a 1-log2-unit higher
MIC as universal, the consequent changes in our results will be
insignificant. Resistance to penicillin will be 13.7%, up from 12.6%,
with only a change in the relative resistance rate of 1.1% and no
change in the complete resistance rate.
Regarding quality control, we regularly use the ATCC strains of
S. pneumoniae (ATCC 49619), Escherichia coli
(ATCC 25922), Haemophilus influenzae (ATCC 49247), and
Pseudomonas aeruginosa (ATCC 27853) (kindly provided by M. Steinhoff of Johns Hopkins University and G. Darmstadt of Washington
University). Blinded observation and checking for internal
reproducibility are routine procedures in our laboratory. Our
laboratory has extensive experience in determining MICs for different
organisms by broth microdilution and E tests (5-10).
Regarding co-trimoxazole resistance of strains isolated from patients
with proven cases of pneumonia, it should be stated that the blood
isolates were from pneumonia patients as mentioned in our previous
paper (4) and, as for serotype distribution, there was no
significant difference with respect to drug resistance when strains
from meningitis and pneumonia patients were compared. In strains from
meningitis and pneumonia patients, the rates of resistance to
penicillin were 13.1% versus 10.6% (P = 0.66),
respectively; similarly, resistance to co-trimoxazole was 63.9% versus
68.1% (P = 0.61), respectively. Further, as for
H. influenzae type b (11), surveillance of
invasive S. pneumoniae cases should focus on meningitis
because the rate of isolation from patients with pneumonia is very low,
in contrast to the situation for meningitis, in which diagnosis is
straightforward and isolation of the organism from cerebrospinal fluid
is simple. We do not have any experience with adult subjects, but the
5.4% resistance rate of the nasopharyngeal isolates from the
immunization clinic versus the 64% resistance rate of community
strains, as mentioned by Lalitha et al., is remarkable. Although they
designated the above groups as hospital and community strains,
respectively, we would be likely to consider both of them community
strains because the children attending the immunization clinic were
healthy and were coming from the community for a short visit (for
vaccination), during which time the nasopharyngeal swabs were
collected. The only difference between these two groups is the
difference in age. On comparison of our cases according to age of the
patient, we also have observed some difference, albeit not as striking
as that observed by Lalitha et al. (3). We observed 61 and
71% co-trimoxazole resistant strains among children up to 1 year old
and from 1 to 5 years old, respectively (P = 0.14).
We will soon begin the isolation of large number of nasopharyngeal
strains (as mentioned in our paper) from a community near Dhaka to test
for possible differences between community and hospital strains.
| |
REFERENCES |
| 1.
|
Jacob, M. R.,
S. Bajaksouzian,
P. C. Appelbaum, and A. Bolmstrom.
1992.
Evaluation of E-test for susceptibility testing of pneumococci.
Diagn. Microbiol. Infect. Dis.
15:473-478.
|
| 2.
|
Jorgensen, J. H.,
A. W. Howell, and L. A. Maher.
1991.
Quantitative antimicrobial susceptibility testing of Haemophilus influenzae and Streptococcus pneumoniae by using the E-test.
J. Clin. Microbiol.
29:109-114[Abstract/Free Full Text].
|
| 3.
|
Lalitha, M. K.,
D. J. Manayani,
L. Priya,
M. V. Jesudason,
K. Thomas, and M. C. Steinhoff.
1997.
E-test as an alternative to conventional MIC determination for surveillance of drug resistant S. pneumoniae.
Indian J. Med. Res.
106:500-503.
|
| 4.
|
Saha, S. K.,
N. Rikitomi,
D. Biswas, et al.
1997.
Serotypes of Streptococcus pneumoniae causing invasive childhood infections in Bangladesh, 1992 to 1995.
J. Clin. Microbiol.
35:785-787[Abstract].
|
| 5.
|
Saha, S. K.,
N. Rikitomi,
M. Ruhulamin,
H. Masaki,
M. Hanif,
M. Islam,
K. Watanabe, et al.
1999.
Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae strains causing childhood infections in Bangladesh, 1993 to 1997.
J. Clin. Microbiol.
37:798-800.
|
| 6.
|
Saha, S. K.,
M. Hanif,
P. Dutta, and M. F. Chowdhury.
1994.
Emergence of high level fluoroquinolone resistant Escherichia coli in Bangladesh.
Int. J. Antimicrob. Agents
4:1-3.
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Saha, S. K.,
W. A. Khan,
M. S. Hoq, et al.
1991.
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Saha, S. K.,
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M. Ruhulamin,
M. Hanif, and I. Maksuda.
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J. Antimicrob. Chemother.
39:554-556[Free Full Text].
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Saha, S. K.
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Antibiotic resistance of Salmonella typhi in Bangladesh.
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33:190-191[Free Full Text].
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| 10.
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Saha, S. K.,
S. Y. Talukder,
M. Islam, and S. Saha.
1999.
A highly ceftriaxone resistant Salmonella typhi in Bangladesh.
Pediatr. Infect. Dis. J.
18:387[Medline].
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| 11.
|
World Health Organization.
1995.
Generic protocol for population based surveillance to assess the local burden of meningitis due to Haemophilus influenzae type B among children less than 5 years old. Field test version, November 1995.
World Health Organization, Geneva, Switzerland.
|
| | | | |
Samir K. Saha*
Department of Microbiology
Bangladesh Institute of Child Health
Dhaka Shishu (Children) Hospital
Dhaka 1207, Bangladesh
|
| | | | |
R. B. Sack
Department of International Health
Johns Hopkins University of Hygiene and Public Health
Baltimore, Maryland
|
| | | | |
K. Matsumoto
T. Nagatake
Department of Internal Medicine
Institute of Tropical Medicine
Nagasaki University
Nagasaki, Japan
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Journal of Clinical Microbiology, August 1999, p. 2743-2744, Vol. 37, No. 8
0095-1137/99/$04.00+0
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