Efficacy and safety of aztreonam versus tobramycin for aerobic gram-negative bacilli lower respiratory tract infections

Efficacy and Safety of Aztreonam Versus Tobramycin for Aerobic Gram-Negative Bacilli Lower Respiratory Tract Infections

JULIE R. RODRIGUEZ, M.D. CARLOS H. RAMIREZ-RONDA, San Juan,

Puerto

Aztreonam therapy was evaluated for the management of 80 patients with gram-negative bacilli lower respiratory tract infections. Study results confirmed its efficacy and safety for this indication.

M.D.

Rico

Infections of the lower respiratory tract, particularly those of nosocomial origin, are associated with a high mortality [1,2]. The source of most of these infections is aerobic &am-negative bacilli, which can lead to gramnegative pneumonia by pharyngeal colonization when an insult and/or aspiration occurs. This colonization has been shown to be transient in healthy subjects [3], but to persist and even increase in the sick patient

PI.

From the Infectious Disease Program and Departments of Research and Medicine, Veteran’s Administration Medical Center and University of Puerto Rico School of Medicine, San Juan, Puerto Rico. This work was supported in part by the Squibb Institute for Medical Research, Princeton, New Jersey. Requests for reprints should be addressed to Dr. Julie Rose Rodriguez, lnfectidus Disease Research (151), Veterans Administration Medical Center, GPO Box 4867, San Juan, Puerto Rico 00936.

42

February

8, 1985

The American

Journal

The management of lower respiratory tract infections caused by gramnegative bacilli traditionally involved the use of an aminoglycoside antibiotic with a beta-lactam agent. However, because the penetration of aminoglycosides into bronchial secretions has been questioned [4], alternative agents are being studied. We initiated a single-blind study, described elsewhere [5], to compare the safety and efficacy of aztreonam, a new beta-lactam agent, with that of tobramycin in our hospitalized patient population, which includes a large number of individuals with hospital-acquired pneumonias and patients falling into the groups at high risk of the development of aerobic gram-negative pneumonia. Eighty patients were randomly assigned to receive either aztreonam or tobramycin for the treatment of gram-negative bacilli lower respiratory tract infections (Tables I and II). Of 53 patients assigned to receive aztreonam, 46 were clinically evaluable and 39 were bacteriologically evaluable at the end of the treatment period. Of the 46 clinically evaluable patients, 41 were considered as having cures, in three patients therapy was considered as failed, and two died during the study period of unrelated causes. Thirty-six of the 39 bacteriologically evaluable patients had cures and in three patients therapy failed. There were 26 clinically evaluable patients in the group assigned to receive tobramycin. Twenty-two patients were considered as having cures, in three patients therapy was considered as failed, and one died of unrelated causes during the study period. There were 18 bacteriologically evaluable patients in the tobramycin group: 17 had cures and in one therapy failed. The most common pathogens isolated from the patients were Klebsiella pneumoniae, Escherichia coli,,and Pseudomonas aeruginosa (Table Ill). All of the isolated organisms were susceptible to both tested antibiotits except for a strain of Pseudomonas cepacia resistant to both tested antimicrobials and a strain of Enterobacter aerogenes and of P. aeruginosa each resistant to aztreonam.

of Medicine

Volume

78 (suppl

2A)

AZTREONAM

TABLE

Administration

I

of Antibiotics’ Tobramycin (n = 26)

Aztreonam (n = 53) 6 g per divided every hours 3 g per (n=l)

Dosage

Mean

duration treatment Range

of (days)

‘All patients received clindamycin antibiotic treatment for 72 hours able.

TABLE

II

240 mg per day divided equally every eight hours

12

11

7 to 27

7 to 26

2.4 g per day. Patients or less were considered

Correlation of Roentgenographic Prior to Therapy with Aztreonam Tobramycin

Lower infiltrates Unilateral Bilateral ,Upper infiltrates Unilateral Bilateral Diffuse Middle lobe infiltrate Perihilar Unilateral Bilateral Total From

day equally eight (n = 52); day

receiving nonevalu-

Findings or

III

patients

assigned

24 14

‘17 3

2.

2

3

3. -

2 7

2 1

4.

3 1 53

0 0 26

5.

13** 1 9** 5** 2 1 3

Enterobacter species Serratia Providencia stuartii Candida diversus Proteus mirabilis Staphylococcus aureus*§ Total

1 2 1 1 1 2 42

measurably

REFERENCES 1.

Klebsiella pneumoniae* Klebsiella oxytoca+ Escherichia coli Pseudomonas aeruginosa+ Pseudomonas species Pseudomonas cepacia* Enterobacter aerogenes”

were

We wish to thank Ms. Carmen G. Camareno for her secretarial assistance and Ms. Minerva Nevarez, M.T., for her technical help.

Tobramycin

Tobramycin

aztreonam,

ACKNOWLEDGMENT

Outcome

Gross PA, Neu HC, Aswapokee P, et al: Deaths from nosocomial infections: experience in a university hospital and a community hospital. Am J Med 1980; 68: 219-223. La Force FM: Hospital-acquired gram-negative rod pneumonias: an overview. Am J Med 1981; 70: 664-669. Ramirez-Ronda CH, Fuxench-Lopez 22, Nevarez M: increased pharyngeal bacterial colonization during viral illness. Arch Intern Med 1981; 141: 1599-1603. Hawley HB, Sers RM, Swartz DR, et al: Tobramycin therapy of pulmonary infections in patients with cystic fibrosis. Curr Ther Res 1974; 16: 414-423. Rodriguez J, Ramirez-Ronda CH, Nevarez M: Efficacy and safety of aztreonam-clindamycin versus tobramycin-clindamycin in the treatment of lower respiratory tract infection caused by aerobic gram-negative bacilli. Antimicrob Agents Chemother (in press).

by Microorganisms,

Susceptibilities

Number of Isolates Isolates

to receive

different between the active treatment groups. According to our study results, aztreonam is safe and effective for the treatment of lower respiratory tract infections caused by aerobic gram-negative bacilli when the organisms are susceptible.

Adreonam

Clinical and Bacteriologic Concentrations (pg/ml)

and HAMIHtL-KVNUA

Few adverse reactions related to the antibiotics were seen. These effects, if present, generally were transient and comparable in both studied groups. Only renal function test results, which were altered in 7.7 percent of patients assigned to receive tobramycin and in none of the

[5].

TABLE

SYMPOSIUM-RODRIGUEZ

Studies,

Minimal

Range

Aztreonam 7**

Tobramycin

4** 4 1 2

0.25 1-4 co.125 ~0.125 0.25

0 0 0 0 18

Cure/Total Atireonam

~0.125-0.25 0.25 GO.125 2-16 2 32 cO.125->128

-

Inhibitory

Tobramycin

Aztreonam

0.25-2 2 0.25-2 0.5-4 0.5-l S128 0.125-4

13113 Ill 919 415 212 213

617 414 414 l/l

0.125-2 2 2 1 0.25

Ill 112 l/l l/l l/l

212 -

-

*Mixed infection, patient had Staphylococcus aureus and Klebsiella pneumoniae. +Mixed infection, patient had Klebsiella oxytoca and Pseudomonas aeruginosa isolated from sputum sample. *The patient had a Pseudomonas cepacia resistant to aztreonam recovered from sputum sample, though patient was considered nonevaluable. §Mixed infection, patient had Staphylococcus &reus recovered with the Enterobacter aerogenes. **Bacteremias: there were four episodes of bacteremias in the aztreonam group: two Klebsiella pneumoniae, one Escherichia coli, and one Pseudomonas aeruginosa; there were two episodes of bacteremia in the tobramycin group: one Escherichia coli and one Klebsiella pneumoniae. Bacteremia was with same pathogen obtained from sputum sample. From [5].

February

8, 1985

The

American

Journal

of Medicine

Volume

78 (suppi

2A)

44