CASE REPORT TwoCases of Severe Bronchiectasis Successfully Treated with a Prolonged Course of Trimethoprim/Sulfamethoxazole Takayuki Honda, Muneharu Hayasaka*, Tsutomu Hachiya*, Keishi Kubo*, Tsutomu Katsuyama and Atsuo Nagata** Twopatients with severe bronchiectasis, one patient without other disease and the other with hyper IgE syndrome, were successfully treated with long-term therapy with low doses oftrimethoprim and sulfamethoxazole (TMP-SMZ).Recurrent respiratory infections with productive cough and high fever were resistant to various antibiotics and often disturbed the patients' activities in daily life. However, they showed marked improvement following TMP-SMZtherapy, which was started for methicillin-resistant Staphylococcus aureus (MRSA)infection. MRSAdisappeared some months later, but Pseudomonas aeruginosa appeared again in the sputum. Both patients, however, have remained free from symptomsfor over one year. (Internal Medicine 35: 979-983, 1996) Key words: hyper IgE syndrome, lower respiratory infection, methicillin-resistant Staphylococcus aureus, Pseudomonasaeruginosa Introduction toms which disturbed his activity in daily life. Hemophilis influenzae and/or Pseudomonas aeruginosa (P. aeruginosa) It has been reported that trimethoprim-sulfamethoxazole were isolated from his sputum. He had received many different (TMP-SMZ) is effective for short-term and long-term use in the antibiotics including ampicillin, piperacillin sodium, treatment of chronic respiratory infections (1, 2). Recently, sultamicillin tosilate, cefazolin sodium, cefotiam hexetil hy- however, TMP-SMZhas not been considered the drug of first drochloride, cefteram pivoxil, clindamycin, ciprofloxacin hy- choice for various bacterial infections due to its side effects and drochloride and ofloxacin. They were sensitive to at least one because of the development of new antibiotics. Wedescribe antibiotic. However,other antibiotics were tried due to repeated here two cases with severe bronchiectasis successfully treated fever. Analysis of his blood showed slight leukocytosis (5,000- with a long-term course of TMP-SMZ. 1 0,800). Erythrocyte sedimentation rate (ESR) had increased to 30-60 mm/h and CRP was 2+ to 4+. Arterial blood gas analysis on November 1 1, 1989, showed hypoxemia (PaO2, 56.8 Torr, Case Report PaCO2, 40.7 Torr; pH 7.410). Various oral antibiotics taken in Case 1 (Fig. 1) rotation were effective only temporarily, and high fever often A 53-year-old male had an operation for chronic sinuitis appeared. Long-term use of erythromycin was added to his when he was 17 years old. He remained well withouthistory of treatment regimen, but the symptoms remained. Methicillin- pulmonary tuberculosis until 48 years of age, when he noted resistant Staphylococcus aureus (MRSA)was isolated from his susceptibility to colds. He visited ourhospital on November12, sputum in May 1 992, and treatment with 6 tablets ofTMP-SMZ 1988, with chief complaints of high fever and productive daily (one tablet included 40 mg ofTMP and 200 mg ofSMZ), cough. A chest roentgenogramshowedreticulonodular shadow to which MRSAwas sensitive, was begun in combination with and bronchial wall thickening in both lung fields and infiltration ciprofloxacin hydrochloride and minocycline. He showed in the right upper field. He was admitted with a diagnosis of marked improvementand becameasymptomatic within several bronchiectasis with acute pneumonia. In the following three days. Heremained free from lower respiratory tract symptoms years, he was again admitted several times for the same symp- after cession of antibiotics other than TMP-SMZ.MRSAdisap- From the Department of Laboratory Medicine and *First Department of Internal Medicine, Shinshu University Hospital, Matsumoto and **SuwaRed Cross Hospital,Suwa Received for publication February 23, 1996; Accepted for publication September 17, 1996 Reprint requests should be addressed to Dr. Takayuki Honda, the Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 , Asahi, Matsumoto390 Internal Medicine Vol. 35, No. 12 (December 1996) 979 Honda et al Antib i o ti c s P O V////////////////////A DIV H El (H Erythromycin K\NN\N\\NNNN\\M TMP-SMZ. ||||l«^ Admission for _ ¥*mmWiM PI pneumonia Ml lailiiilli ID 1111 Fever 30~| I I I days/month 15- [ 1 I j 0J 1 1 1 1 1 1 1 1 1 ! mmz mmm ESR CRP WBCX103 OWBC (mm/h) (+) (///I) -i 12-j à"ESR 20- 0- 2- \||^1^»^"^ '89.6 i 9i 12i '90.3 i-i-i-i-i-i-i6 9 12 '91.3 6 9 121-i'92.3 61-i-i-i-i-i-i-i-r9 12 '93.3 6 9 12 '94.3 6 Figure 1. Clinical course of Case 1. peared and only normal habitants were isolated from sputum within a few months. P. aeruginosa, however, appeared again in the sputumwithout exacerbation of the respiratory symp- toms. The dose of TMP-SMXwas reduced to 3 tablets/day in December 1992. ESR and CRP fell within the respective normal ranges. Arterial blood gas analysis also improved (PaO2, 77.2 Torr; PaCO2 46.2 Torr; pH 7.390). When TMP-SMZ was reduced to one tablet/day in June 1993, his temperature rose to 38.5°C with an increase of white blood cells and elevation of CRPand ESR, although a chest roentgenogram did not show new consolidation (Fig. 2). The dose of TMP-SMZwas in- creased to 2 tablets/day and his temperature was reduced. He then continued to take the same dose daily for one year, and no side effects were observed. Whenthe dose of TMP-SMZwas again reduced gradually and stopped in June 1994, he noted fever and an increase in productive cough. TMP-SMZtherapy was restarted and the symptomsdisappeared immediately. He has remainedfree from symptomson a regimenof one tablet of TMP-SMZper day without adverse reactions to date. Case 2 (Fig. 3) Figure2. A chest roentgenogram of case 1 showing A 34-year-old female had suffered from abscesses on vari- bronchial thickening with reticulonodular shadow. ous regions of her body without pain. She was diagnosed as having hyper IgE syndrome with a serum IgE level of over 10,000 lU/ml when she was 13 years old. She had an operation for a peritoneal abscess at the age of 17 years. She was also 980 Internal Medicine Vol. 35, No. 12 (December 1996) TMP/SMZTherapy for Bronchiectasis 1iiiiiiii iiii ii i i i IgE (IU/ml) [ Admission for pneumonia 3- " / ^^"^^^ | Fever 0-| , 1 f , , , , , , , , , , , j '89 '90 '91 '92 '93 '94 '95 Figure 3. Clinical course of Case 2. admitted for treatment of myelitis of the right femur and an abscess on the upperpharynx at20 and 30 years old. From1989, whenshe was 30 years old, she often cameto our hospital with respiratory infection and high fever. She was diagnosed as having bronchiectasis and was treated with various antibiotics. She had no history of chronic sinuitis or pulmonary tuberculo- sis. A chestroentgenogram (Fig. 3) and CT scans showed cystic lesions and bronchial thickening in the right upper lobe and bronchial thickening in both lower lobes. These respiratory symptoms often disturbed her activity in daily life and she was admitted several times over the following years. Methicillin- sensitive Staphylocossus aureus (MSSA)and P. aeruginosa were isolated from sputum. In 1991, MRSAwas first detected in sputum and TMP-SMZwas added to the other antibiotics in her treatment regimen. After initiation of TMP-SMZtreatment, the symptomsof respiratory infection were reduced. The dose of TMP-SMZwas reduced and stopped because we had no experience regarding its long-term use and the available drug information emphasized its side effects. On February 9, 1993, she again visited our hospital with fever and productive cough, Figure4. A chest roentgenogram of case 2 showing and she was treated with oral cephalosporin notTMP-SMZ.She patchy infiltration shadows in both lung fields with bronchial developed the above symptomsand then dyspnea appeared thickening predominantly in the right upper field. within three days. Chest roentgenogram showed patchy infiltra- tion shadows in both lung fields (Fig. 4) and MRSAwas isolated from blood. She was diagnosed with adult respiratory distress and 2 tablets/day have been continued as a prophylaxis against syndrome accompanied by MRSAsepsis, which was causedby further infections. P. aeruginosa was often isolated from spu- MRSApneumonia. She recovered after intensive treatment tum, although she has remained free from symptoms of respi- with vancomycin, habekacin, minomycin and TMP-SMZto ratory infection. The level of serum IgE gradually fell to 2,000 which MRSAis sensitive. Subsequently, TMP-SMZwas used IU/ml. at a dose of 4 tablets/day without other antibiotics for one year Internal Medicine Vol. 35, No. 12 (December 1996) 981 Honda et al cases were reported in Swedenbetween 1976 and 1985. The Discussion motality rate for patients with bicytopenia was reported as 6%, and 52%for those with tricytopenia (1 1). Most patients Anumber of studies have shown that TMP-SMZis an with blood dyscrasias showed improvement when TMP-SMZ effective agent for treatment of respiratory tract infections (2- therapy was stopped or folic acid treatment started (13). 4). TMP-SMZis not, however, considered the drug of first It is difficult to determine the appropriate dose ofTMP-SMZ choice, because many other antibiotics have been developed for individual patients. For simultaneous primary prophylaxis and used for various bacterial infections. of Pneumocystis carinii pneumonia and toxoplasmosis in pa- Most Staphylococcus aureus strains, regardless of methicil- tients infected with HIV, TMP-SMZadministered three times lin susceptibility, have shown susceptibility to TMP-SMZ.The per week(160 mg-800mgorally twice a day) is an effective and Japan Cooperative Clinical Study Group reported that therapy well-tolerated regimen ( 14), and for the prevention of sponta- with TMP-SMZwas effective in 86 of 109 patients with neous bacterial peritonitis in patients with cirrhosis, one dou- Staphylococcus aureus infection (5). However, resistance to ble-strength TMP-SMZtablet daily, five times a week (Monday TMP-SMZin staphylococci may be rising; it has been reported through Friday), was efficacious, safe, and cost effective (15).