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Antimicrobial Agents and Chemotherapy, February 1999, p. 436-437, Vol. 43, No. 2
0066-4804/99/$00.00+0
LETTERS TO THE EDITOR
Cefepime versus Ceftriaxone for Empiric Treatment of
Hospitalized Patients with Community-Acquired Pneumonia
 |
LETTER |
We read with interest the report of the clinical trial by Zervos
et al. (5) in which cefepime was compared with ceftriaxone for empiric treatment of hospitalized patients with community-acquired pneumonia. Although that paper presented some interesting findings, there are several methodological flaws with the study that we would
like to comment on.
The first problem relates to patient eligibility. The criteria for
hospitalization of patients (3, 4) were not clearly defined.
It appears that patients were included in the trial without radiological evidence of pneumonia, even though it has been suggested that a chest film showing infiltrates is necessary to establish the
diagnosis of pneumonia (1). Moreover, the authors apparently also considered as a criterion for patient eligibility the presence of
bacteria susceptible to cefepime and ceftriaxone. This seems rather
risky since it has been shown that it is seldom possible to reach a
specific etiologic diagnosis by roentgenography alone (4).
We also found that in Table 2, which describes the characteristics of
pneumonia presented by the patients at the time of entry in the study,
the severity of pneumonia is classified as mild, moderate, or severe,
but definitions for these categories are not provided.
A second difficulty encountered by the reader is that, in evaluating
efficacy, the authors define the category "improvement" as
"improvement of one or more signs and symptoms of pneumonia without a
complete resolution but a lack of progression of radiographic findings," and consider it a favorable clinical response. This would
mean that if a patient improved in just one symptom, say for example,
cough, this would be regarded as a "favorable clinical response."
We feel that the category "improvement" makes little medical sense
in dealing with pneumonia. In addition, in the General Guidelines for
the Evaluation of New Anti-Infective Drugs for the Treatment of
Respiratory Tract Infections (2), this category is not
included in the definition of clinical response. Moreover, it is
not clear how the category "improvement" was determined for
patients which were included in the study without a previous chest film.
Thirdly, we are also concerned about the fact that in this study some
patients were treated concomitantly with several other antibiotics.
Although treatment with erythromycin and metronidazole can be justified
in cases where atypical pathogens or anaerobes are suspected, there
were seven patients who received six additional antibiotics. Despite
the fact that the authors suggest that antibiotic treatment had little
impact on the efficacy of the drugs studied, it is difficult to
classify these patients with respect to clinical response. Besides, the
authors never mention when these additional antibiotics where added or
what the criterion was for adding them. We feel that the criteria for
patient evaluation in this study are debatable. For example, what
exactly do the authors mean when they say that "Seven additional
patients who received additional antimicrobial agents were approved by
the sponsor as evaluable"?
Finally, this study also lacks a clearly stated hypothesis and, thus, a
sample size calculation.
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FOOTNOTES |
*
Phone: 34 93 291 90 18
Fax: 34 93 291 91 78
E-mail: 1273{at}hsp.santpau.es
| |
REFERENCES |
| 1.
|
Barlett, J. G., and L. M. Mundy.
1995.
Community-acquired pneumonia.
N. Engl. J. Med.
333:1618-1624[Free Full Text].
|
| 2.
| Chow, A. W., C. B. Hall, J. O. Klein,
R. B. Kammer, R. D. Meyer, and J. S. Remington.
1992. General guidelines for the evaluation of new anti-infective drugs
for the treatment of respiratory tract infections. Clin. Infect. Dis.
15(Suppl. 1):S62-S88.
|
| 3.
|
Levison, M. E.
1998.
Pneumonia, including necrotizing pulmonary infections (lung abscess), p. 1437-1445.
In
Harrison's principles of internal medicine, 14th ed. McGraw-Hill, New York, N.Y.
|
| 4.
|
Penn, R. L., and R. F. Betts.
1996.
Lower respiratory tract infections, p. 258-349.
In
R. E. Reese, and R. F. Betts (ed.), A practical approach to infectious diseases, 4th ed. Little, Brown and Company, Toronto, Canada.
|
| 5.
|
Zervos, M.,
M. Nelson, and The Cefepime Study Group.
1998.
Cefepime versus ceftriaxone for empiric treatment of hospitalized patients with community-acquired pneumonia.
Antimicrob. Agents Chemother.
42:729-733[Abstract/Free Full Text].
|
| | | | |
Javier Borja
Francesc Jané*
Department of Clinical Pharmacology
Hospital de la Santa Creu i Sant Pau
Avgda. Sant Antoni Ma Claret, 167
08025 Barcelona
Spain
|
| |
AUTHOR'S REPLY |
We disagree with Borja and Jané regarding the alleged
methodological flaws in our study.
Regarding eligibility, previously published definitions of pneumonia
(1, 2) were used. Evidence of community-acquired pneumonia
consisted of documentation of at least two of the following three
groups of signs and symptoms (i) fever (temperature greater than
38°C) or hypothermia (temperature less than 36°C); (ii) purulent sputum (>25 polymorphonuclear leukocytes and <10 squamous
cells/low-power field), leukocytosis (>10,000
leukocytes/mm3), worsening arterial oxygen gradients in
relation to baseline measurements, or newly developed hypoxia; and
(iii) evidence of pulmonary involvement probably due to the presence of
bacteria susceptible to cefepime and ceftriaxone (radiologic findings
consistent with the diagnosis of aspiration pneumonia, lobar pneumonia,
or diffuse unilateral or bilateral pneumonia and/or signs of pulmonary consolidation or pneumonia on physical examination). All patients had
pulmonary infiltrates (Table 2 in our article). We agree that definitions used for severity of illness should have been included.
Regarding improvement not being a useful category, patients were
considered to have improved if there was a lack of progression in all
positive findings on chest radiography but improvement in one or more
signs and symptoms of pneumonia without a complete resolution.
Regarding concomitant antibiotics, as stated in our article,
erythromycin and metronidazole were administered for
atypical pathogens and anaerobes, respectively. Patients that
received concomitant antibiotics were analyzed separately.
Although certain concomitant antibiotics (primarily erythromycin
and metronidazole) were allowed during this trial, concomitant
treatment appeared to have little impact on the rate of favorable
clinical response in the clinically evaluated patients (cefepime group,
100% with concomitant antibiotics and 92.9% without; ceftriaxone
group, 92.9% with concomitant antibiotics and 100% without).
Regarding sample size determination, we acknowledged in Discussion that
this trial did not include sufficient numbers of patients to detect
subtle differences in efficacy and safety between cefepime and
ceftriaxone; the data reported, however, support the conclusion that
cefepime and ceftriaxone are therapeutically comparable for the empiric
treatment of community-acquired pneumonia in hospitalized patients.
These two agents were equally effective against the pathogens in this
study, and both were associated with a low rate of adverse effects.
Finally, we feel the objective of this study was clear and obvious; it
was, as stated, to evaluate the comparative safety and efficacy of
cefepime and ceftriaxone for community-acquired pneumonia.
| |
REFERENCES |
| 1.
|
Bartlett, J. G.,
R. F. Breiman,
L. A. Mandell, and T. M. File, Jr.
1998.
Community-acquired pneumonia in adults: guidelines for management.
Clin. Infect. Dis.
26:811-838[Medline].
|
| 2.
| Chow, A. W., C. B. Hall, J. O. Klein,
R. B. Kammer, R. D. Meyer, and J. S. Remington.
1992. General guidelines for the evaluation of new anti-infective drugs
for the treatment of respiratory tract infections. Clin. Infect. Dis.
15(Suppl. 1):S62-S88.
|
| | | | |
Marcus J. Zervos
William Beaumont Hospital
Royal Oak, Mich.
|
Antimicrobial Agents and Chemotherapy, February 1999, p. 436-437, Vol. 43, No. 2
0066-4804/99/$00.00+0
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