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Treatment of Pulmonary Melioidosis with Combination of Trimethoprim and Sulfamethoxazole
focal ulcerative bronchitis and extensive interstitial pneumonitis are most likely the result of infection w i t h the bacillus of Legionnaires' disease. The histopathologic picture i n our patient's specimen from pulmonary biopsy differs from that w h i c h is typical of acute bacterial pneumonia and is more consistent w i t h changes characteristically found when viruses, rickettsiae, chlamydiae (bedsoniae), or Mycoplasma pneumoniae organisms are the infecting agents. » Since the histologic patterns observed i n such infections are nonspecific, Legionnaires' disease may perhaps be added to the list of infections causing pulmonary interstitial infiltration w i t h mononuclear cells; further differentiation among the diseases i n this group b y histopathologic examination is at present not reliable. 4
5
REFERENCES 1 Fraser D W , Tsai TR, Orenstein W , et al: Legionnaires' disease: Description of an epidemic of pneumonia. Ν Engl J Med 297:1189-1197,1977 2 Follow-up on respiratory infection. Morbidity Mortality Weekly Rep 25:308,1976 3 Follow-up: Respiratory disease—Philadelphia. Morbidity Mortality Weekly Rep 25:270-275,1976 4 Spencer H : Pathology of the Lung (2nd ed). New York, Pergamon Press, 1968 5 Heard BE, Wright GP: The lungs. In Symmers WSC (ed) : Systemic Pathology (2nd ed). New York, ChurchillLivingstone, 1976, pp 322-327
Treatment of Pulmonary Melioidosis FIGURE 3. Specimen from pulmonary biopsy, showing inter stitial pneumonitis. Alveolar walls are thickened and edema tous and are lined with proliferating type 2 pneumocytes. Lymphocytes and plasma cells predominate i n inflammatory reaction, and alveolar spaces are choked with macrophages (hematoxylin-eosin, χ 500). titer of fluorescent antibody for the bacterium of Legion naires' disease. DISCUSSION Open lung biopsy after approximately ten days of clinical illness showed acute bronchitis w i t h focal ulcera tion and diffuse acute interstitial pneumonitis. Areas of ulcerative bronchitis ( F i g 2 ) included focal necrosis of bronchial epithelium, w i t h preservation of the basement membrane. The pulmonary parenchyma ( F i g 3 ) showed interstitial pneumonitis, w i t h lymphocytes and plasma cells predominating i n the thickened edematous alveolar walls, w h i c h were covered b y proliferating type 2 pneu mocytes. M a n y alveoli were filled w i t h macrophages, neutrophils, and proteinaceous exudate. N o hyaline membranes were seen. W e consider i t unlikely that these pathologic findings were the result of superinfection w i t h bacterial or other pathogens i n view of the normal results of bactériologie and serologic studies, and the patient had not received therapy w i t h supplemental oxygen i n the amount usually associated w i t h histologic changes of toxicity. Thus, the
222 FULLER ET AL
with Combination of Trimethoprim and Sulfamethoxazole* Maj Philip B. Fuller, MC, USAF; Maf David E. Fisk, MC, USAF; Col. Richard B. Byrd, MC, USAF, F.C.C.P.; George A. Griggs, M.D., F.C.C.?.;** and Copt Michael R. Smith, USAF Treatment w i t h a combination o f trimethoprim and sul famethoxazole proved lifesaving i n a patient w i t h pul monary melioidosis after therapeutic failure occurred w i t h other antibiotics to which the organisms were sen sitive in vitro. Antagonistic interaction o f drugs oc curred when the combination o f trimethoprim and sulfa methoxazole was given along w i t h other antibiotics. The combination o f trimethoprim and sulfamethoxazole should be considered a major addition to the pharma cologic armamentarium for the treatment of pulmonary melioidosis. •From the Department of Pulmonary Disease, United States Air Force Medical Center Scott, Scott Air Force Base, Illinois. The views expressed herein are those of the authors and do not necessarily reflect the views of the United States Air Force or the Department of Defense. ••Presently at Veterans Administration Hospital, Little Rock, Ark. Reprint requests: Dr. Fuller, USAF Hospital, Scott AFB, Illinois 62225
CHEST, 74: 2, AUGUST, 1978
T
he search for the ideal drug i n the treatment of melioidosis continues. The organism, Pseudomonas psetulomaUei, is not only resistant to therapy w i t h many antibiotics but clinically may fail to respond to those drugs to w h i c h i t is sensitive in vitro.1 I t has been shown that therapy w i t h the combination of trimethoprim and sulfamethoxazole is effective in vitro, and one patient w i t h pulmonary melioidosis has been treated successfully w i t h this pharmacologic combination. ' W e have re cently seen a patient whose infection failed to respond to all other antibiotics to w h i c h in vitro sensitivity was shown but whose illness d i d resolve w i t h therapy w i t h trimethoprim and sulfamethoxazole; however, the thera peutic response occurred only when this combination was given alone ( i n order to avoid pharmacologic an tagonism) and i n four times the conventional dosage. 2
3
CASE REPORT This 23-year-old aircraft mechanic was referred to our hospital in June 1976 for evaluation of a persistent pulmonary infection. The patient first became i l l in November 1975, with the sudden onset of cough, hemoptysis, chills, and fever. A patchy infiltrate with cavities was seen in the left upper lobe on the chest x-ray film. Three months of intermittent therapy with various anti biotics, including methicillin, gentamicin, penicillin, and clindamycin, gave inconsistent relief of symptoms. Because of continued severe hemoptysis, the patient underwent left upper lobectomy in February 1976; however, within a few weeks the cough and fever recurred, and he was referred to our hospital. Physical examination revealed only rales in the left upper pulmonary field. The chest x-ray film showed loss of volume of the left lung and cavitary infiltrates. Further history revealed that the patient had originally become i l l in the Philippine Islands. His duties there included the washing of aircraft wheel wells which were dusty from previous landings in Southeast Asia. These facts, together with the clinical history, suggested the diagnosis of melioido sis, and Ρ pseudomallei was promptly isolated from the sputum. Complement-fixation tests for melioidosis were eventually positive at a titer of 1:256. Initial minimum inhibitory concentrations for the following antibiotics were noted: tetracycline, 4/ig/ml; chlorampheni col, 16/Ag/ml; kanamycin, 32/Ag/ml; and trimethoprim and sulfamethoxazole, l/ug/ml and 19/¿g/ml, respectively. There was resistance to all other drugs tested. Therapy with tetracycline ( 500 mg four times daily ) was begun, and the patient improved symptomatically. Growth of Ρ pseudomallei on weekly cultures of sputum changed from "heavy" to "light." During the second month of therapy, symptoms recurred, cultures became strongly positive, and the chest x-ray films showed progression of the left-sided infiltrate, with a new infiltrate in the right lung. Finally, after several episodes of massive hemoptysis, sin gle drugs and multidrug combinations of tetracycline (750 mg orally every six hours), chloramphenicol (25 mg/kg of body weight intravenously every six hours), and kanamycin ( 1 gm daily intramuscularly) were administered over three weeks, again without clinical response. Bacteriostatic activity in the serum was noted up to dilutions of 1:8 with various combinations of drugs, but none showed bactericidal activity. Antagonism of drugs occurred when therapy with trimetho
CHEST, 74: 2, AUGUST, 1978
prim and sulfamethoxazole was added to the combination of the other three drugs, resulting in the loss of all bacteriostatic activity. Therapy with the combination of trimethoprim ( 160 mg) and sulfamethoxazole (800 mg) orally twice daily alone also proved unsuccessful. The dosages of these two drugs were then increased to 240 mg and 1,200 mg, respectively, four times daily. Bactericidal activity to dilutions of 1:8 were then noted, with no previous pharmacologic therapy having produced bactericidal activity. Dramatic resolution of symp toms promptly occurred, and cultures of sputum were nega tive within three weeks. Treatment was continued for a total of seven months, with rapid resolution of the pulmonary infiltrates and only minimal left-sided fibrosis remaining. DISCUSSION
Therapy with trimethoprim and sulfamethoxazole in this patient with melioidosis appears to have been lifesaving, since administration of the other more commonly used drugs failed to control the infection. Bactericidal levels of tetracycline, chloramphenicol, and kanamycin could not be attained; and, indeed, the patient never showed more than a temporary response to therapy with these medications. Furthermore, it was only with the high dosage of 240 mg of trimethoprim and 1,200 mg of sulfamethoxazole four times daily that in vitro bac tericidal activity could be attained. It is of interest that John3 reported a bactericidal titer of 1:4 with a dosage of 160 mg of trimethoprim and 800 mg of sulfamethoxa zole twice daily, with clinical cure of his patient with melioidosis. A previous laboratory investigation has suggested that pharmacologic antagonism might occur when therapy with a combination of antibiotics is used; and, indeed, that did appear to occur in our patient.4 When therapy with a combination of trimethoprim and sulfamethoxa zole was added to the regimen of tetracycline, chlor amphenicol, and kanamycin, no bacteriostatic or bac tericidal effect could be noted on testing of the serum. Only when the combination of trimethoprim and sulfa methoxazole was used as a single agent was a bac tericidal effect demonstrable. This observation has prac tical implications, since many authorities have suggested the use of therapy with multiple drugs, particularly in those with disseminated melioidosis. Our patient was also interesting from the epidemio logic standpoint, as melioidosis is rare in the Philippine Islands. We believe that his infection likely came from cleaning the wheel wells of aircraft which had been used on earthen runways of the Southeast Asian subcontinent, a major endemic area. An aerosol of the dust from the wheel wells was undoubtedly created when they were hosed down, and aerosols are known to induce the disease.5 This patient also illustrates the importance of consid ering this disease in any patient with a respiratory infection who has been exposed to the endemic area. Specimens should be plated on both routine and Sabouraud's agar; and if plates are not kept for 72 to 96 hours, the characteristic wrinkled colonies will not be noted, and the organism may be misidentified. Another TREATMENT OF PULMONARY MELIOIDOSIS 223
clue to the etiology of his illness was missed early i n the patient's disease when a report was made of Ρ aerugi nosa on culture, w h i c h on disk testing showed sensitivity to tetracycline and kanamycin, w i t h resistance to gentamicin. This unusual data on sensitivity should sug gest infection w i t h Ρ pseudomallei. T h e combination of t r â n e t h o p r i m and sulfamethoxazole should be considered a primary d r u g i n the treatment of pulmonary melioidosis, particularly i n those whose condition shows in vitro resistance to treatment w i t h tetracycline or fails to improve on a trial of therapy w i t h this drug. Studies of sensitivity should be obtained initially and should be repeated at intervals d u r i n g therapy. Dosage may be adjusted on the basis of bactericidal levels. A C K N O W L E D G M E N T : We wish to thank Dr. Jay Sanford of the School of Medicine, Uniformed Services University of the Health Sciences, for his advice in the management of this patient and the Center for Disease Control, Atlanta, for providing the data on minimum inhibitory concentrations. REFERENCES 1 Everett ED, Nelson RA: Pulmonary melioidosis. Am Rev Respir Dis 112:331-340, 1975 2 Everett ED, Kishimoto RX: In vitro sensitivity of 33 strains of Pseudomonas pseudomallei to trimethoprim and sulfamethoxazole. J Infect Dis 128 (suppl):539, 1973 3 John JF Jr: Trimethoprim-sulfamethoxazole therapy i n pulmonary melioidosis. Am Rev Respir Dis 114:1021-1025, 1976 4 Eickhoff TC, Bennett JV, Haynes PS, et al: Pseudomonas pseudomallei: Susceptibility to chemotherapeutic agents. J Infect Dis 121:95-102, 1970 5 Green RN, Tuffnell PG: Laboratory acquired melioidosis. Am J Med 44:599-605, 1968
Bacterial Endocarditis on a Prosthetic Valve* Oral Treatment with Amoxicillin Moshe Lidji, Μ.Ό.; Ethan Rubinstein, M.D.; and Heskel Samra, M.D. A patient with endocarditis due to Streptococcus faecalis on an aortic valvular prosthesis was successfully treated using large oral doses of amoxicillin concurrently with intramuscular administration of streptomycin. Oral therapy was employed because of a persistent reaction to intravenously administered antibiotics. Oral therapy for bacterial endocarditis occurring on an artificial valve may be attempted as a last resort when all other accepted therapeutic measures have failed.
rrihe current recommended treatment for patients w i t h endocarditis due to Streptococcus faecalis on •From the Infectious Diseases Unit and the Department of Medicine, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
224 LIDJI, RUBINSTEIN, SAMRA
prosthetic cardiac valves is intravenous therapy w i t h high doses of penicillin or ampicillin, w i t h the addition of an aminoglycoside. Surgical replacement of the infected prosthesis is recommended when medical ther apy fails. ' Despite these measures, a high mortality has been noted for prosthetic valvular endocarditis. " Whereas endocarditis o œ u n i n g on a natural valve has been successfully treated w i t h oral therapy, ' no such information is available œ n c e r n i n g the therapy for bacterial endocarditis on a prosthetic valve. A patient w i t h endocarditis due to S faecalis on an artificial aortic valve who was unable to tolerate any intravenous therapy was treated successfully w i t h large oral doses of amoxicillin and intramuscular administration of streptomycin. This combination of drugs yielded a satisfactory bactericidal effect on the serum, w h i c h correlated w i t h the recovery of the patient. 1-7
5
6
4
8
7
9
CASE REPORT A 63-year-old man was admitted to the Chaim Sheba Medical Center, Tel-Hashomer, Israel, because of the recent onset of left hemiparesis following one month of fever and malaise. The patient had undergone an aortic valvular replacement and aneurysmectomy of the ascending aorta for syphilitic cardiovascular disease three years prior to this admission. His postoperative course had been uneventful, and he remained in good health until the present illness. The patient denied any dental or genitourinary manipulations. On admission the patient appeared to be in no acute distress. His temperature was 38.4°C ( 1 0 1 . 1 F ) , the blood pressure was 180/80 mm Hg, and the pulse rate was 68 beats per minute. A grade 3/6 systolic murmur was heard over the aortic area; the murmur did not radiate. A small petechia was observed on the patient's left thumb. Neurologic examination revealed mild paresis of the left arm and leg. The findings from the rest of the physical examination were normal. No other signs of endocarditis were observed. The results of laboratory tests were as follows: hemoglobin level, 8.7 gm/100 m l ; hematocrit reading, 23 percent; white blood cell count, 9,600/cu mm, with a shift to the left; erythrocyte sedimentation rate, 25 mm in the first hour; V D R L test, negative; and Treponema pallidum immobilization test, positive. The rest of the chemical findings on the blood and cerebrospinal fluid were normal. Six consecutive cultures of blood grew S faecalis, and the minimum inhibitory concentration of ampicillin was 1.75¿tg/ml and of amoxicillin 0.5/ag/ml. The minimum inhibitory concentration of streptomycin was lOO^g/ml. Synergism was demonstrated both for the combination of ampicillin and streptomycin and for amoxicillin and streptomycin. The patient was started on therapy with 12 gm of ampicillin intravenously daily and 1 gm of streptomycin intramuscularly. Very severe thrombophlebitis developed rapidly in all of the veins into which ampicillin was introduced. Intravenous therapy with ampicillin was therefore changed to oral administration of 24 gm of ampicillin daily, and therapy with streptomycin was continued; however, the bactericidal effect in the serum varied between 1:2 and 1:16 on various occasions. Repeated attempts to administer medication intravenously failed because of immediately recurring grave thrombophlebitis. While the patient was receiving oral therapy with ampicillin (total, ten days), atrial fibrillation appeared, and his fever persisted. Therefore, oral administrae
CHEST, 74: 2, AUGUST, 1978
5
REFERENCES 1 Fraser D W , Tsai TR, Orenstein W , et al: Legionnaires' disease: Description of an epidemic of pneumonia. Ν Engl J Med 297:1189-1197,1977 2 Follow-up on respiratory infection. Morbidity Mortality Weekly Rep 25:308,1976 3 Follow-up: Respiratory disease—Philadelphia. Morbidity Mortality Weekly Rep 25:270-275,1976 4 Spencer H : Pathology of the Lung (2nd ed). New York, Pergamon Press, 1968 5 Heard BE, Wright GP: The lungs. In Symmers WSC (ed) : Systemic Pathology (2nd ed). New York, ChurchillLivingstone, 1976, pp 322-327
Treatment of Pulmonary Melioidosis FIGURE 3. Specimen from pulmonary biopsy, showing inter stitial pneumonitis. Alveolar walls are thickened and edema tous and are lined with proliferating type 2 pneumocytes. Lymphocytes and plasma cells predominate i n inflammatory reaction, and alveolar spaces are choked with macrophages (hematoxylin-eosin, χ 500). titer of fluorescent antibody for the bacterium of Legion naires' disease. DISCUSSION Open lung biopsy after approximately ten days of clinical illness showed acute bronchitis w i t h focal ulcera tion and diffuse acute interstitial pneumonitis. Areas of ulcerative bronchitis ( F i g 2 ) included focal necrosis of bronchial epithelium, w i t h preservation of the basement membrane. The pulmonary parenchyma ( F i g 3 ) showed interstitial pneumonitis, w i t h lymphocytes and plasma cells predominating i n the thickened edematous alveolar walls, w h i c h were covered b y proliferating type 2 pneu mocytes. M a n y alveoli were filled w i t h macrophages, neutrophils, and proteinaceous exudate. N o hyaline membranes were seen. W e consider i t unlikely that these pathologic findings were the result of superinfection w i t h bacterial or other pathogens i n view of the normal results of bactériologie and serologic studies, and the patient had not received therapy w i t h supplemental oxygen i n the amount usually associated w i t h histologic changes of toxicity. Thus, the
222 FULLER ET AL
with Combination of Trimethoprim and Sulfamethoxazole* Maj Philip B. Fuller, MC, USAF; Maf David E. Fisk, MC, USAF; Col. Richard B. Byrd, MC, USAF, F.C.C.P.; George A. Griggs, M.D., F.C.C.?.;** and Copt Michael R. Smith, USAF Treatment w i t h a combination o f trimethoprim and sul famethoxazole proved lifesaving i n a patient w i t h pul monary melioidosis after therapeutic failure occurred w i t h other antibiotics to which the organisms were sen sitive in vitro. Antagonistic interaction o f drugs oc curred when the combination o f trimethoprim and sulfa methoxazole was given along w i t h other antibiotics. The combination o f trimethoprim and sulfamethoxazole should be considered a major addition to the pharma cologic armamentarium for the treatment of pulmonary melioidosis. •From the Department of Pulmonary Disease, United States Air Force Medical Center Scott, Scott Air Force Base, Illinois. The views expressed herein are those of the authors and do not necessarily reflect the views of the United States Air Force or the Department of Defense. ••Presently at Veterans Administration Hospital, Little Rock, Ark. Reprint requests: Dr. Fuller, USAF Hospital, Scott AFB, Illinois 62225
CHEST, 74: 2, AUGUST, 1978
T
he search for the ideal drug i n the treatment of melioidosis continues. The organism, Pseudomonas psetulomaUei, is not only resistant to therapy w i t h many antibiotics but clinically may fail to respond to those drugs to w h i c h i t is sensitive in vitro.1 I t has been shown that therapy w i t h the combination of trimethoprim and sulfamethoxazole is effective in vitro, and one patient w i t h pulmonary melioidosis has been treated successfully w i t h this pharmacologic combination. ' W e have re cently seen a patient whose infection failed to respond to all other antibiotics to w h i c h in vitro sensitivity was shown but whose illness d i d resolve w i t h therapy w i t h trimethoprim and sulfamethoxazole; however, the thera peutic response occurred only when this combination was given alone ( i n order to avoid pharmacologic an tagonism) and i n four times the conventional dosage. 2
3
CASE REPORT This 23-year-old aircraft mechanic was referred to our hospital in June 1976 for evaluation of a persistent pulmonary infection. The patient first became i l l in November 1975, with the sudden onset of cough, hemoptysis, chills, and fever. A patchy infiltrate with cavities was seen in the left upper lobe on the chest x-ray film. Three months of intermittent therapy with various anti biotics, including methicillin, gentamicin, penicillin, and clindamycin, gave inconsistent relief of symptoms. Because of continued severe hemoptysis, the patient underwent left upper lobectomy in February 1976; however, within a few weeks the cough and fever recurred, and he was referred to our hospital. Physical examination revealed only rales in the left upper pulmonary field. The chest x-ray film showed loss of volume of the left lung and cavitary infiltrates. Further history revealed that the patient had originally become i l l in the Philippine Islands. His duties there included the washing of aircraft wheel wells which were dusty from previous landings in Southeast Asia. These facts, together with the clinical history, suggested the diagnosis of melioido sis, and Ρ pseudomallei was promptly isolated from the sputum. Complement-fixation tests for melioidosis were eventually positive at a titer of 1:256. Initial minimum inhibitory concentrations for the following antibiotics were noted: tetracycline, 4/ig/ml; chlorampheni col, 16/Ag/ml; kanamycin, 32/Ag/ml; and trimethoprim and sulfamethoxazole, l/ug/ml and 19/¿g/ml, respectively. There was resistance to all other drugs tested. Therapy with tetracycline ( 500 mg four times daily ) was begun, and the patient improved symptomatically. Growth of Ρ pseudomallei on weekly cultures of sputum changed from "heavy" to "light." During the second month of therapy, symptoms recurred, cultures became strongly positive, and the chest x-ray films showed progression of the left-sided infiltrate, with a new infiltrate in the right lung. Finally, after several episodes of massive hemoptysis, sin gle drugs and multidrug combinations of tetracycline (750 mg orally every six hours), chloramphenicol (25 mg/kg of body weight intravenously every six hours), and kanamycin ( 1 gm daily intramuscularly) were administered over three weeks, again without clinical response. Bacteriostatic activity in the serum was noted up to dilutions of 1:8 with various combinations of drugs, but none showed bactericidal activity. Antagonism of drugs occurred when therapy with trimetho
CHEST, 74: 2, AUGUST, 1978
prim and sulfamethoxazole was added to the combination of the other three drugs, resulting in the loss of all bacteriostatic activity. Therapy with the combination of trimethoprim ( 160 mg) and sulfamethoxazole (800 mg) orally twice daily alone also proved unsuccessful. The dosages of these two drugs were then increased to 240 mg and 1,200 mg, respectively, four times daily. Bactericidal activity to dilutions of 1:8 were then noted, with no previous pharmacologic therapy having produced bactericidal activity. Dramatic resolution of symp toms promptly occurred, and cultures of sputum were nega tive within three weeks. Treatment was continued for a total of seven months, with rapid resolution of the pulmonary infiltrates and only minimal left-sided fibrosis remaining. DISCUSSION
Therapy with trimethoprim and sulfamethoxazole in this patient with melioidosis appears to have been lifesaving, since administration of the other more commonly used drugs failed to control the infection. Bactericidal levels of tetracycline, chloramphenicol, and kanamycin could not be attained; and, indeed, the patient never showed more than a temporary response to therapy with these medications. Furthermore, it was only with the high dosage of 240 mg of trimethoprim and 1,200 mg of sulfamethoxazole four times daily that in vitro bac tericidal activity could be attained. It is of interest that John3 reported a bactericidal titer of 1:4 with a dosage of 160 mg of trimethoprim and 800 mg of sulfamethoxa zole twice daily, with clinical cure of his patient with melioidosis. A previous laboratory investigation has suggested that pharmacologic antagonism might occur when therapy with a combination of antibiotics is used; and, indeed, that did appear to occur in our patient.4 When therapy with a combination of trimethoprim and sulfamethoxa zole was added to the regimen of tetracycline, chlor amphenicol, and kanamycin, no bacteriostatic or bac tericidal effect could be noted on testing of the serum. Only when the combination of trimethoprim and sulfa methoxazole was used as a single agent was a bac tericidal effect demonstrable. This observation has prac tical implications, since many authorities have suggested the use of therapy with multiple drugs, particularly in those with disseminated melioidosis. Our patient was also interesting from the epidemio logic standpoint, as melioidosis is rare in the Philippine Islands. We believe that his infection likely came from cleaning the wheel wells of aircraft which had been used on earthen runways of the Southeast Asian subcontinent, a major endemic area. An aerosol of the dust from the wheel wells was undoubtedly created when they were hosed down, and aerosols are known to induce the disease.5 This patient also illustrates the importance of consid ering this disease in any patient with a respiratory infection who has been exposed to the endemic area. Specimens should be plated on both routine and Sabouraud's agar; and if plates are not kept for 72 to 96 hours, the characteristic wrinkled colonies will not be noted, and the organism may be misidentified. Another TREATMENT OF PULMONARY MELIOIDOSIS 223
clue to the etiology of his illness was missed early i n the patient's disease when a report was made of Ρ aerugi nosa on culture, w h i c h on disk testing showed sensitivity to tetracycline and kanamycin, w i t h resistance to gentamicin. This unusual data on sensitivity should sug gest infection w i t h Ρ pseudomallei. T h e combination of t r â n e t h o p r i m and sulfamethoxazole should be considered a primary d r u g i n the treatment of pulmonary melioidosis, particularly i n those whose condition shows in vitro resistance to treatment w i t h tetracycline or fails to improve on a trial of therapy w i t h this drug. Studies of sensitivity should be obtained initially and should be repeated at intervals d u r i n g therapy. Dosage may be adjusted on the basis of bactericidal levels. A C K N O W L E D G M E N T : We wish to thank Dr. Jay Sanford of the School of Medicine, Uniformed Services University of the Health Sciences, for his advice in the management of this patient and the Center for Disease Control, Atlanta, for providing the data on minimum inhibitory concentrations. REFERENCES 1 Everett ED, Nelson RA: Pulmonary melioidosis. Am Rev Respir Dis 112:331-340, 1975 2 Everett ED, Kishimoto RX: In vitro sensitivity of 33 strains of Pseudomonas pseudomallei to trimethoprim and sulfamethoxazole. J Infect Dis 128 (suppl):539, 1973 3 John JF Jr: Trimethoprim-sulfamethoxazole therapy i n pulmonary melioidosis. Am Rev Respir Dis 114:1021-1025, 1976 4 Eickhoff TC, Bennett JV, Haynes PS, et al: Pseudomonas pseudomallei: Susceptibility to chemotherapeutic agents. J Infect Dis 121:95-102, 1970 5 Green RN, Tuffnell PG: Laboratory acquired melioidosis. Am J Med 44:599-605, 1968
Bacterial Endocarditis on a Prosthetic Valve* Oral Treatment with Amoxicillin Moshe Lidji, Μ.Ό.; Ethan Rubinstein, M.D.; and Heskel Samra, M.D. A patient with endocarditis due to Streptococcus faecalis on an aortic valvular prosthesis was successfully treated using large oral doses of amoxicillin concurrently with intramuscular administration of streptomycin. Oral therapy was employed because of a persistent reaction to intravenously administered antibiotics. Oral therapy for bacterial endocarditis occurring on an artificial valve may be attempted as a last resort when all other accepted therapeutic measures have failed.
rrihe current recommended treatment for patients w i t h endocarditis due to Streptococcus faecalis on •From the Infectious Diseases Unit and the Department of Medicine, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
224 LIDJI, RUBINSTEIN, SAMRA
prosthetic cardiac valves is intravenous therapy w i t h high doses of penicillin or ampicillin, w i t h the addition of an aminoglycoside. Surgical replacement of the infected prosthesis is recommended when medical ther apy fails. ' Despite these measures, a high mortality has been noted for prosthetic valvular endocarditis. " Whereas endocarditis o œ u n i n g on a natural valve has been successfully treated w i t h oral therapy, ' no such information is available œ n c e r n i n g the therapy for bacterial endocarditis on a prosthetic valve. A patient w i t h endocarditis due to S faecalis on an artificial aortic valve who was unable to tolerate any intravenous therapy was treated successfully w i t h large oral doses of amoxicillin and intramuscular administration of streptomycin. This combination of drugs yielded a satisfactory bactericidal effect on the serum, w h i c h correlated w i t h the recovery of the patient. 1-7
5
6
4
8
7
9
CASE REPORT A 63-year-old man was admitted to the Chaim Sheba Medical Center, Tel-Hashomer, Israel, because of the recent onset of left hemiparesis following one month of fever and malaise. The patient had undergone an aortic valvular replacement and aneurysmectomy of the ascending aorta for syphilitic cardiovascular disease three years prior to this admission. His postoperative course had been uneventful, and he remained in good health until the present illness. The patient denied any dental or genitourinary manipulations. On admission the patient appeared to be in no acute distress. His temperature was 38.4°C ( 1 0 1 . 1 F ) , the blood pressure was 180/80 mm Hg, and the pulse rate was 68 beats per minute. A grade 3/6 systolic murmur was heard over the aortic area; the murmur did not radiate. A small petechia was observed on the patient's left thumb. Neurologic examination revealed mild paresis of the left arm and leg. The findings from the rest of the physical examination were normal. No other signs of endocarditis were observed. The results of laboratory tests were as follows: hemoglobin level, 8.7 gm/100 m l ; hematocrit reading, 23 percent; white blood cell count, 9,600/cu mm, with a shift to the left; erythrocyte sedimentation rate, 25 mm in the first hour; V D R L test, negative; and Treponema pallidum immobilization test, positive. The rest of the chemical findings on the blood and cerebrospinal fluid were normal. Six consecutive cultures of blood grew S faecalis, and the minimum inhibitory concentration of ampicillin was 1.75¿tg/ml and of amoxicillin 0.5/ag/ml. The minimum inhibitory concentration of streptomycin was lOO^g/ml. Synergism was demonstrated both for the combination of ampicillin and streptomycin and for amoxicillin and streptomycin. The patient was started on therapy with 12 gm of ampicillin intravenously daily and 1 gm of streptomycin intramuscularly. Very severe thrombophlebitis developed rapidly in all of the veins into which ampicillin was introduced. Intravenous therapy with ampicillin was therefore changed to oral administration of 24 gm of ampicillin daily, and therapy with streptomycin was continued; however, the bactericidal effect in the serum varied between 1:2 and 1:16 on various occasions. Repeated attempts to administer medication intravenously failed because of immediately recurring grave thrombophlebitis. While the patient was receiving oral therapy with ampicillin (total, ten days), atrial fibrillation appeared, and his fever persisted. Therefore, oral administrae
CHEST, 74: 2, AUGUST, 1978