Use of Imipenem in the Treatment of Pulmonary Nocardiosis

which perforation into the left side of the chest occurred. The clinical presentation of traumatic diaphragmatic hernia is either acute or delayed in its appearance. Late presentations as in our patient may occur months or years after the initial injury.' The patient may complain of chronicalxlominal pain and/or chest symptoms or develop features of intestinal obstruction. Indeed, our patient reported nausea, vomiting of bilious material, and abdominal pain approximately 72 h before the diagnosis was made. Her inconsequential stab wound to the left side of her lower rib cage two years prior to her present hospital admission ruptured her diaphragm. The pleural peritoneal pressure gradient allowed migration of the abdominal structures into her chest cavity that may have been compounded by the presence of a gravid uterus and the surgical manipulation during the cesarean section. Subsequently, a portion of the transverse colon became strangulated in the left side of the chest and ruptured with passage of feces and intestinal gas into the pleural cavity. The sudden development ofleft-sided chest pain following intractable vomiting and the appearance of a hydropneumothorax on roentgenogram suggested the diagnosis of an esophageal rupture. Indeed, an infected pleural fluid with a high amylase content was consistent with that diagnosis. However, the appearance of the material aspirated from the chest after placement of the chest tube, namely its feculent odor and Gram stain that revealed a polymicrobial flora, raised the question of intestinal rupture. Moreover, when the culture 24 h later revealed a mixed flora of enterics and enterococci, the diagnosis of a ruptured abdominal viscus was made. It is easy to see how the diagnosis ofan esophageal rupture can be confused with that of perforation of bowel through a diaphragmatic hernia. The history of penetrating injury to the chest together with signs and symptoms of intestinal obstruction and the development of a pneumothorax should at least suggest traumatic diaphragmatic hernia as a diagnostic possibility. Physical examination and plain roentgenograms of the chest and abdomen are seldom diagnostic and radiopaque contrast studies of the gastrointestinal tract are usually needed to make the diagnosis.' With esophageal rupture, oral contrast usually reveals a defect in the esophagus. With rupture of the intestine into the left side of the chest, oral contrast studies will be normal. Treatment consists of surgical intervention with resection of necrotic bowel and repair of the diaphragmatic defect. Our patient with posttraumatic diaphragmatic hernia presented as a tension fecal pneumothorax several months or years after an apparently minor injury. This complication of a diaphragmatic hernia should be included in the differential diagnosis of spontaneous pneumothorax. REFERENCES

1 Bush CH, Margulies R. Traumatic diaphragmatic hernia and intestinal obstruction due to penetrating trunk wounds. South Med J 1990; 83:1347-50 2 Radin DR, Ray MJ, Halls JM. Strangulated diaphragmatic hernia with pneumothorax due to colopleural fistula. AJR 1986; 146:32122 3 Brown GL, Richardson OJ. Traumatic diaphragmatic hernia a continuing challenge. Ann Thorac Surg 1985; 66:682-89 4 Carter BN, Guseffi J, Kelson B. Traumatic diaphragmatic hernia. AJR 1951; 65:56-72

Use of Imlpenem In the Treatment of Pulmonary Nocardiosis· William UJ, M.D.; and Kenneth V. I. Rolston, M.D.

A case of pulmonary nocardiosis with empyema in a 55year-old man with macroglobulinemic lymphoma is presented. Treatment with imipeoem followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) resolved his symptoms andcleared the roentgenographic abnormalities. This case illustrates the clinical potential of imipeoem against Nocardia. (Chat 1993; 103:951-52)

I

TMP-SMX

=trimethoprim-sulfamethouzole

I

ocardiosis is an important opportunistic infection in N patients with neoplastic diseases, recipients of organ transplants, and those receiving treatment with corticoste-

roids 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 trimethoprimsulfamethoxazole (fMJlSMX) 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-Yeal'"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"C)developed. His medical history was significant for treatment with various chemotherapeutic agents since the diagnosis oflymphoma in 1984and 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 pulse dexamethasone. At the time of hospital admission, he had a temperature of39.3°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 6,3OOIcu 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 UIL. His chest roentgenogram showed left lower lobe infiltrates with blunting of the left costophrenic angle. The patient was initially 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 associated loculated pleural etrusion on the left side. A diagnostic thoracentesis was performed, and Gram-positive branching rods, subsequently identified as Nocardia arteroides, were found in the pleural fluid. This organism, which also grew in the sputum, was susceptible to imipenem, TMP-SMX, sulfisoxazole, tobramycin, amikacin, lcana-From the Department of Medical SpeciaIties, Section of Infectious Diseases, The University of Texas M.D. Anderson Cancer Center, Houston. Reprint requests: Dr: Rolston, Umoersity of Texas MD Anderson Cancer Center; 1515 Holcombe Blvd, Houston, TX 77030 CHEST I 103 I 3 I MARCH, 1993

951

Table I-Drog Susceptibility of the Nocardia asteroides laolate by the Agar Diak Diffusion Method· Antibiotic Imipenem Amikacin Kanamycin Tobramycin Doxycycline Cefoxitin

Ctprofloxaein

TMP-SMX Sulfisoxazole Erythromycin

Concentration Tested, mWL 8

20 20

5 5

30

1 0.519.5 50

5

Resultt S S S S S S R S S R

*Tests were performed by the City Health Department of Houston, Texas. tS = susceptible; R = resistant. mycin,cefoxitin, and doxycycline ('Iable1). The susceptibilitytesting was performed by the City Health Department of Houston using the agar disk diffusion method.' 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 antibioticsand wassubsequentlysent homeon a regimen of oral TMP-SMX. A chest roentgenogram after three months sbowed 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 oforalantibioticshowedno recurrence offeveror 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." However, failures with these agents have been reported" 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.' Routine susceptibility testing for Nocardia is recommended because of the variable in vitro activity ofvarious 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' provides results that are comparable with those obtained by the broth microdiIution minimum inhibitory concentration (MIC) method," 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 N()C(lrdia species have shown that cefuroxime, cefotaxime, ceftnasone, amikacin, netilmicin, minocycline, imipenem, and some carboxyquinolones are also active against Nocardia species..... 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.· In a similar animal model study of N asteroides pneumonia, combination of amikacin and imipenem, and several broad-spectrum cephalosporins were 952

superior to sulfonamides in eradicating Nocardia from lung tissue. 10 Recently, Krone et al" reported the case of a 72-year old woman with nocardia! cerebral abscess who was treated with imipenem and amikacin. Her symptoms resolved although she later required a craniotomy to remove a wellencapsulated abscess. Ruppert et all" reported a case of a biopsy- and culture-proven pulmonary nocardiosis in a 67year-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." 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" and Ruppert et al'" 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 Nocardiaspecies. J Infect Dis 1977; 135:568-76 2 Berkey P, Bodey GP. Nocardial infection in patients with neoplasticdiseases. Rev Infect Dis 1989; 2:407-12 3 Cockerill FR, Edson RS, Roberts GD, WaldorfJC. Trimethoprim/sulfamethoxazole-resistant Nocardia asteroides causing multiple hepatic abscesses. AmJ Med 1984; 77:558-60 4 Rodriguez JL, BarrioJL, Pitchenik AE. Pulmonary nocardiosis in the acquired immunodeficiency syndrome. Chest 1986; 90:912-14 5 Wallace RJ, Steele Le. Susceptibilitytesting of Nocardiaspecies for the clinical laboratory. Diagn Microbiol Infect Dis 1988; 9:155-66 6 Gutmann L, Goldstein F\v, Kitzis MD, Hantefort B, Darmon C, AcarJF. Susceptibility of Nocardia asteroides to46antibiotics, including 22 ~-Iactams. Antimicrob Agents Chemother 1983; 23:248-51 7 Gombert ME, Aulicino TM, duBouchet L, Berkowitz LB. Susceptibility of Nocardia asteroides to new quinolones and ~-lactams. Antimicrob AgentsChemother 1987; 31:2013-14 8 Berkey P, Moore D, Rolston K. In vitro susceptibilities of Nocardia species to newer antimicrobial agents. Antimicrob AgentsCbemotber 1988; 32:1078-79 9 Gombert ME, duBouchet L, Aulicino TM, Berkowitz LB. Antimicrobial synergismin the therapy ofexperimentalcerebral nocardiosis. Antimicrob AgentsChemother 1989; 23:39-43 10 Gombert ME, Berkowitz LB, Aulicino TM, duBouchet L. Tberapy of pulmonary nocardiosis in immunocompromised mice. Antimicrob AgentsChemother 1990; 34:1766-68 11 Krone A, Schaal Kp, Brawanski A, Schuknecht B. Nocardial 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 lmipenem in Pulmonary Nocardiosis (Lo, Rolston)