Imipenem

A case of pulmonary nocardiosis with empyema in a 55-year-old man with macroglobulinemic lymphoma is presented. Treatment with imipenem followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) resolved his symptoms and cleared the roentgenographic abnormalities. This case illustrates the clinical potential of imipenem against Nocardia.

Nocardiosis is an important opportunistic infection in patients with neoplastic diseases, recipients of organ transplants, and those receiving treatment with corticosteroids and various chemotherapeutic agents. Whereas in vitro studies have shown that other antimicrobials are active against Nocardia species, the treatment of choice for this infection has been with the sulfonamides and trimethoprim-sulfamethoxazole (TMP-SMX) since clinical experience with alternative agents has been minimal. We present a case of pulmonary nocardiosis with empyema that responded to treatment with imipenem.

CASE REPORT

A 55-year-old man with a well-differentiated macroglobulinemic lymphoma involving the lungs and the stomach was referred to us for evaluation of a nonproductive cough, malaise, and intermittent low-grade fever that had persisted for two months. Several days prior to hospital admission, his cough became productive and a high fever (39 [degrees] C) developed. His medical history was significant for treatment with various chemotherapeutic agents since the diagnosis of lymphoma in 1984 and an autologous bone marrow transplantation in 1989 following chemotherapy with melphalan and total body irradiation. He went into remission after the bone marrow transplantation and was subsequently placed on a regimen of maintenance therapy with interferon alpha and pluse dexamethasone.

At the time of hospital admission, he had a temperature of 39.3 [degrees] C. He was not in any distress, and the results of his physical examination were unremarkable except for diminished breath sounds and a few rales at the left lung base. His white blood cell count was 6,300/cu mm with a predominance of polymorphonuclear leukocytes. Results of blood chemistry studies were within normal limits except for a mild elevation of lactate dehydrogenase to 308 U/L. His chest roentgenogram showed left lower lobe infiltrates with blunting of the left costophrenic angle.

The patient was initally treated with intravenous aztreonam and vancomycin to provide broad antimicrobial coverage. However, because of persistent fever, aztreonam was replaced with imipenem on the third day of hospitalization. Computed tomography of the chest revealed pulmonary infiltrates with an assoicated loculated pleural effusion on the left side. A diagnostic thoracentesis was performed, and Gram-positive branching rods, subsequently identified as Nocardia asteroides, were found in the pleural fluid. This organism, which also grew in the sputum, was susceptible to imipenem, TMP-SMX, sulfisoxazole, tobramycin, amikacin, kanamycin, cefoxitin, and doxycycline (Table 1). The susceptibility testing was performed by the City Health Department of Houston using the agar disk diffusion method.[1]

The patient became afebrile within 48 h after starting therapy with imipenem and his cough and sputum production gradually resolved. He was completely asymptomatic after ten days of parenteral antibiotics and was subsequently sent home on a regimen of oral TMP-SMX. A chest roentgenogram after three months showed a significant decrease in the amount of the left pleural effusion and by the fifth month of treatment with TMP-SMX, only residual pleural thickening and minor parenchymal scarring were evident. Follow-up four weeks after completion of a seven-month course of oral antibiotic showed no recurrence of fever or respiratory symptoms.

DISCUSSION

The mainstay of therapy for nocardial infection has been the sulfonamides. TMP-SMX has been shown to be clinically effective as well.[2] However, failures with these agents have been reported[3] and in addition, bone marrow toxicity and skin rash secondary to these agents can occur, particularly among AIDS patients who are also at risk for this infection because of their impaired cellular immunity. These side effects often require discontinuation of treatment with the sulfa-containing drugs.[4] Routine susceptibility testing for Nocardia is recommended because of the variable in vitro activity of various antimicrobial agents against this pathogen. Although a standardized susceptibility test is not available at present, the disk diffusion method as described by Wallace et al[1] provides results that are comparable with those obtained by the broth microdilution minimum inhibitory concentration (MIC) method.[5] Nevertheless, one must still be aware that the results of susceptibility tests do not always correlate with clinical outcome.

Several in vitro susceptibility studies of Nocardia species have shown that cefuroxime, cefotaxime, ceftriaxone, amikacin, netilmicin, minocycline, imipenem, and some carboxyquinolones are also active against Nocardia species.[6-8] In a mouse model of cerebral nocardiosis, the combination of imipenem and cefotaxime and of imipenem and TMPSMX were found to be the most effective in reducing the bacterial colony counts in the brain. The combinations were superior to cefotaxime and TMP-SMX alone but not superior to imipenem alone.[9] In a similar animal model study of N asteroides pneumonia, combination of amikacin and imipenem, and several broad-spectrum cephalosporins were superior to sulfonamides in eradicating Nocardia from lung tissue.[10]

Recently, Krone et al[11] reported the case of a 72-year old woman with nocardial cerebral abscess who was treated with imipenem and amikacin. Her symptoms resolved although she later required a craniotomy to remove a well-encapsulated abscess. Ruppert et al[12] reported a case of a biopsy-and culture-proven pulmonary nocardiosis in a 67-year-old man treated successfully with a 26-day course of imipenem and amikacin followed by a six-month course of oral TMP-SMX.

Previous in vitro susceptibility testing at our institution has demonstrated excellent activity of imipenem against Nocardia species.[8] To our knowledge, this report cites the first case of pulmonary nocardiosis to respond to imipenem used alone. Although imipenem therapy was started empirically in this patient, it was continued after a definitive diagnosis was made because of the patient's rapid clinical response even before therapy with TMP-SMX was started. Our experience as well as that of Krone et al[11] and Ruppert et al[12] suggest that imipenem either as a single agent or in combination with other antimicrobial agents could be used as an alterative for the treatment of nocardiosis in patients when sulfonamides fail or are not tolerated. Further clinical experience is needed to fully evaluate the efficacy of imipenem in this situation.

REFERENCES

[1] Wallace RJ, Septimus EJ, Musher DM, Martin RR. Disk diffusion susceptibility testing of Nocardia species. J Infect Dis 1977; 135:568-76

[2] Berkey P, Bodey GP. Nocardial infection in patients with neoplastic diseases. Rev Infect Dis 1989; 2:407-12

[3] Cockerill FR, Edson RS, Roberts GD, Waldorf JC. Trimethoprim/sulfamethoxazole-resistant Nocardia asteroides causing multiple hepatic abscesses. Am J Med 1984; 77:558-60

[4] Rodriguez JL, Barrio JL, Pitchenik AE. Pulmonary nocardiosis in the acquired immunodeficiency syndrome. Chest 1986; 90:912-14

[5] Wallace RJ, Steele LC. Susceptibility testing of Nocardia species for the clinical laboratory. Diagn Microbiol Infect Dis 1988; 9:155-66

[6] Gutmann L, Goldstein FW, Kitzis MD, Hantefort B, Darmon C, Acar JF. Susceptibility of Nocardia asteroides to 46 antibiotics, including 22 [beta]-lactams. Antimicrob Agents Chemother 1983; 23:248-51

[7] Gombert ME, Aluicino TM, duBouchet L, Berkowitz LB. Susceptibility of Nocardia asteroides to new quinolones and [beta]-lactams. Antimicrob Agents Chemother 1987; 31:2013-14

[8] Berkey P, Moore D, Rolston K. In vitro susceptibilities of Nocardia species to newer antimicrobial agents. Antimicrob Agents Chemother 1988; 32:1078-79

[9] Gombert ME, duBouchet L, Aulicino TM, Berkowitz LB. Antimicrobial synergism in the therapy of experimental cerebral nocardiosis. Antimicrob Agents Chemother 1989; 23:39-43

[10] Gombert ME, Berkoiwitz LB, Aulicino TM, duBouchet L. Therapy of pulmonary nocardiosis in immunocompromised mice. Antimicrob Agents Chemother 1990; 34:1766-68

[11] Krone A, Schaal KP, Brawanski A, Schuknecht B. Noicardial cerebral abscess curved with imipenem/amikacine and enucleation. Neurosurg Rev 1989; 12:333-40

[12] Ruppert S, Reinold HM, Jipp P, Schroter G, Egner E, Schaal KP. Successful antibiotic treatment of a pulmonary infection with Nocardia asteroides. Dtsch Med Wochenschr 1988; 113:1801-05

COPYRIGHT 1993 American College of Chest Physicians
COPYRIGHT 2004 Gale Group