[Correlation between pulmonary pharmacokinetics and pharmacodynamics support the hypothesis of the usefulness of ceftazidime at a single 1g daily dose in the treatment of bacterial exacerbation of chronic obstructive bronchopneumonia with moderate functional damage].
BACKGROUND
Experimental studies have shown that cephalosporins have an antibacterial effect in vivo even when their levels are above MIC for only 40-50% of dosing intervals, whereas maximum killing is obtained when concentrations are above MIC for 60-70% of the time. Since most patients treated with antibiotics have neutrophils and other natural defence mechanisms, it is likely that a bacteriostatic effect should be sufficient to induce an effective therapeutic response.


METHODS
Given that in the potential sites of lung infection ceftazidime reaches significantly higher levels than the MIC of the most commonplace respiratory pathogens, even 8-12 hours after the administration of 1 g i.m., the authors evaluated the efficacy of treatment of renewed acute episodes of COPD using this antibiotic at a dose of 1 g once a day. In order to do this, 20 outpatients were enrolled in the study, half of whom presented moderate bronchial obstruction (FEV1 = 50-70% of theoretical) whereas the remainder presented marked bronchial obstruction (FEV1 = < 50% of theoretical).


RESULTS
The 10 patients with moderate obstruction at the time of enrollment, who presented Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis as causal agents in the sputum (Escherichia coli was only isolated in one patient), showed a marked improvement following treatment with 1 g ceftazidime one a day. A real or presumed eradication of the causal microorganism was observed in all subjects. Treatment with ceftazidime at the dose of 1 g/die once a day was much less effective in patients with marked bronchial obstruction. Treatment was successful in 7 out of 10 subjects, but 2 of them relapsed within 2 weeks. In this second group, Pseudomonas aeruginosa was found in the sputum of 3 patients; one of the patients showed a persistence of the bacterium after ceftazidime treatment, and another presented reinfection 12 days after the end of treatment. The two patients in whom Staphylococcus aureus was isolated did not benefit from ceftazidime treatment at this dosage. One subject who initially presented Streptococcus pneumoniae in his sputum and was then thought to have recovered, underwent a new acute episode caused by Moraxella catarrhalis 2 weeks after the suspension of ceftazidime treatment.


CONCLUSIONS
The therapeutic responses observed during this study suggest the possibility of using ceftazidime in a single daily dose of 1 g i.m. to treat those patients with exacerbations of COPD who only present moderately impaired functional symptoms. On the contrary, this type of therapeutic approach must be used with extreme caution in subjects with marked functional damage, although a satisfactory clinical response may be obtained in some cases. However, the small number of patients included in this study does not allow firm conclusions to be drawn. Only a study involving a larger group of patients could provide the necessary information to confirm the hypothesis for treatment put forward by the authors.
Cazzola
M
M
Divisione di Pneumologia ed Allergologia, Ospedale A. Cardarelli, Napoli.
Noschese
P
P
Vinciguerra
A
A
Di Perna
F
F
Califano
C
C
Berra
A
A
D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D001996:Bronchopneumonia / Q000188:drug therapy* / Q000382:microbiology; D002442:Ceftazidime / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D012008:Recurrence
D002511:Cephalosporins; D002442:Ceftazidime