|Ann. Medit. Burns Club - vol. VI - n. 2 - June 1993
AZTHREONAM IN THE TREATMENT OF PNEUMONIA IN MAJOR
BURN PATIENTS: A PRELIMINARY STUDY
Mariscal-Sistiaga F, Lenguas-Portero
F, Galvan-Guijo B., Ahon-Elizaide J.M., Gomez-Tello V., Herruz-Cabrera R.*, Garcia
Hospital La Paz, Madrid, Spain
* Universidad Autônoma de Madrid
SUMMARY. During 1990, 20 cases
of nosocomial pneumonia in critical bum patients were treated in the Critical Bum Unit of
the La Paz Hospital in Madrid. Fourteen of these patients were cured while four of them
experienced a clinical improvement. The pathogen microorganism was eliminated in ten
cases, and five controls were always negative, coinciding with clinical improvements and
cures. No adverse effects were perceived. We conclude that azthreonam, in association with
vancomycin and teichoplanin, is a very effective drug for treatment of nosocomial
pneumonia in severe bum patiens, for which tolerance, both local and systemic, is
Azthreonarn is a monobactalamic
antibiotic with a specific activity spectrum with respect to all aerobic gram-negative
bacteria, including Pseudomonas aeruginosa. It achieves very similar minimum
inhibitor concentrations (MIC) and minimum bactericidal concentrations (MBQ. It acts by
fixation to certain proteins in the bacterial membrane, the inhibition pro-ducing
elongation and lysis of the bacterium; it also extends its bactericidal action to
granulocyte phagocyted micro-organisms, improving phagocytosis.
It shows a high degree of resistance to lytic enzymes (beta-lactamases) present in the
periplasmic space of gram-negative bacteria, both with regard to chromosomic and plasmidic
resistance. It does not induce production of beta-lactamases.
Azthreonam penetrates the organic tissues and liquids, where it reaches far higher
concentrations than the MIC of the main Enterobacteriaceae. This antibiotic enjoys very
good tolerance, with few side effects necessitating interruption of its administration.
Azthreonam is indicated in treatment of infections of the urinary, gynaco-obstetrical and
lower respiratory tract, the abdomen, bones, joints, skin and soft tissue, in
non-complicated gonorrhoea and septicaemia, and in post-surgical infection when the
infections are caused by gram-negative aerobic bacteria (1). A critical bum patient is one
whose bum extent, depth, mechanism and site and/or previous pathology presents a serious
life threatening risk requiring admission to special Burn Units (2). The bum patient
behaves like an immunodeficient patient (3, 4). The loss of the outer limit of the body,
the skin, which constitutes an effective barrier against most microorganisms (5), the
stress brought on by repeated surgical operations (6), the plasma and blood transfusions
(7), and the metabolic alterations suffered lead to a Temporary Secondary Immunodeficiency
Syndrome (8). All this favours development of septic complications (infections of the
lower respiratory tract, septicaemia, urinary infections, infections of the skin, etc.),
which become the fundamental cause of death (9), even in the presence of appropriate local
and systemic treatments, by causing the failure of all antimicrobial therapy attempts (10,
Material and methods
During 1990-91, 20 seriously burned
patients with nosocomial pneumonia (two also with concomitant urinary infection) were
admitted to the Serious Bums Unit of the Hospital La Paz in Madrid and studied
prospectively. They were treated with azthreonam (2g/6h intravenously): 6 on monotherapy
and 14 on associated therapy (12 with vancomycin, I with cephalothin, and I with
vancomycin and amphotericin B). In cases where vancomycin was the associated antibiotic,
the patients' plasmatic levels were monitored in order to adjust the dose and to avoid
In accordance with established inclusion criteria, patients of both sexes were admitted
suffering from nosocomial pneumonia, the aetiology of which was known or suspected to be
caused by gram-negative micro-organisms requiring antibiotic treatment for a minimum
period of 5 days. Burn patients with associated urinary infection were also admitted.
Exclusion criteria eliminated from the study patients under 14 years of age, patients with
terminal disease which prevented completion of the treatment cycle, patients who in the
opinion of the investigators could not be evaluated, patients suffering from established
renal failure, patients whose infection was caused by micro-organisrns resistant to the
antibiotic, patients with a history of anaphylactic reaction to the antibiotic studied or
to other betalactamic antibiotics, women during lactation and granulocytopenic patients
Assessment of the bum area extent was made by the rule of nines (12) and the infection
criteria were those of the Centers for Disease Control (13). Analytical, radiological and
bacteriological controls were carried out every three days, with the exception of certain
cases in which some intervals were shortened for justifiable reasons.
Clinical controls were carried out on a daily basis, and were continued for a period of
two weeks after patient discharge.
Clinical assessment of response to treatment
Cure: remission of clinical and
radiological manifestations caused by the infectious disease.
Improvement: favourable clinical and radiological response, with persistence of some
clinical manifestations related to the infectious disease. Failure: absence of a
response, with persistence of clinical and radiological manifestations of equal intensity.
Bacteriological assessment of response to treatment
Elimination of causative micro-organism: sterilization
of cultures obtained from the infection site.
Selection: emergence of a new pathogen agent different from the original one, at the same
or another infection site, during the treatment period, or during the immediate
post-treatment period, together with clinical manifestations thereof.
Failure: persistence of the same pathogen agent during treatment.
Out of the 20 patients treated, 14
(70%) were male, and 6 (30%) female, with ages ranging from 16 to 73 years (mean 42.9
years). Of these patients, 9 had suffered no known previous pathology, 4 had a psychiatric
case history (2 were drug addicts), 3 suffered from chronic alcoholism, 3 from obesity, I
from arterial hypertension, I from epilepsy, I from toxic syndrome, I from diabetes
mellitus, and one was HIV positive; several of these pathologies were concomitant in some
patients. On admission, we observed in addition to the bums 6 smoke inhalation syndromes,
2 polytraumatisms, I bronchoaspiration, I diabetic decompensation, and I arsenic
intoxication. Table I illustrates the injury mechanisms. The percentage of body area
burned varied between 25% and 85% (mean 53.75%). By depth the injuries were: 11
superficial dermic, 19 deep dermic and 16. subdermic. These involved various anatomical
sites, depending on the case.
The prevailing micro-organisms were: It Pseudomonas aeruginosa, 2 Acinetobacter,
2 Staphylococcus aureus, I Escherichia coli, I Pseudomonas cepacia, and I Candida
Albicans, in pneumonia cases, and 1 Escheriqhia coli and I Proteus
mirabilis, in concomitant urinary infections.
Thirteen patients required prolonged mechanical ventilation for more than 7 days.
From the clinical point of view, 14 cures (70%) were achieved, 4 (20%) improvements and 1
(5%) failure, while in I case (5%) the result could not be evaluated. There were 3 deaths,
one of them secondary to the infectious process, and two caused by problems alien to the
|Table 1 Injury
Bacteriologically speaking, there were 10 (50%) negative
results and 4 (20%) selections (Candida albicans, Staphylococcus aureus, Acinetobacter and
Pseudomonas aeruginosa resistant to azthreonam). Cultures were negative in 5 (25%)
patients, and one patient could not be evaluated because of death before the successive
No adverse effects were observed.
The prevailing germs Pseudomonas
aeruginosa, Staphylococcus aureus, Acinetobacter and Escherichia coli isolated
in our patients do not differ from those isolated in most serious Burn Units (14, 15).
The clinical results obtained (14 cures and 4 improvements) mean that azthreonarn was
effective in 90% of the pathologies treated. With regard to bacteriological results, we
must point out that the 5 cases with negative cultures corresponded to patients in whom
the samples were taken during azthreonam treatment. Since clinical success was achieved in
these patients, we consider that this bacteriological group must be linked to that of
negative results. This corresponds to 15 (75%) bacteriological successes.
It is to be expected that prolonged use of azthreonam in monotherapy may select Staphylococcus,
as was the case in two of our patients, since the antimicrobial spectrum is limited,
being effective only against. gram-negative germs (1).
The good bacteriological and clinical
results obtained in our study and the importance of preserving renal function intact
suggested to us the use of azthreonam in the treatment of nosocomial pneumonia in patients
with serious burns, rather than other potentially nephrotoxic antimicrobial agents.
In view of the selection of germs observed, and taking into account that the antimicrobial
spectrum of azthreonam is limited to gram-negative microorganisms, we consider that this
antibiotic should be administered in association with other efficient agents against Staphylococcus
(vancomycin, teichoplanin, etc.).
Azthreonarn is a very active drug against gramnegative pathogens that cause nosocomial
pneumonia in critical bum patients, with an excellent local and systemic tolerance.
RESUME. Pendant 1990, 20 cas de pneumonie
nosocomiale chez des grand brûles ont été treités dans le Centre des Brûlés de
l'Hôpital La Paz, Madrid. De ces patients 14 ont guéri et 4 ont eu une amélioration
clinique. Le micro-organisme pathogène a été éliminé en 10 cas, et 5 contrôles ont
été toujours négatifs, en correspondance d'améliorations et guérisons cliniques. Les
auteurs D'ont pas observé d'effets défavorables, Ils concluent que fazthreonam, en
association avec la vancomycine et la teicoplanine, est un médicament très efficace pour
le traitement de la pneumonie nosocomiale chez les grands brûlés et pour lequel il y a
une excellente tolérance locale et systémique.
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