Journal of Infection (1991) 22, 241-245
B a c t e r a e m i a and f u n g a e m i a in adults w i t h cystic fibrosis J. V. Fahy,* M. T. Keoghan, E.J. Crummy and M. X. FitzGerald Adult Cystic Fibrosis Centre, St Vincent's Hospital, Elm Park, Dublin 4, Republic of Ireland Accepted for publication 25 October 299o
Summary The incidence of bacteraemia and fungaemia was determined in 29 adults with cystic fibrosis (CF) during 50 consecutive admissions to hospital for management of infective exacerbations of pulmonary disease. Blood was drawn for aerobic, anaerobic and fungal cultures from all patients who were febrile on admission or who became febrile during treatment. The population included eight patients who had indwelling venous access systems in situ. The overall incidence of positive blood cultures in febrile patients was 3"5 % [95 % confidence interval (C.I.), I-6 %]. We recorded one case of Pseudomonas aeruginosa bacteraemia and two cases of Candida albicans fungaemia. The patient with P. aeruginosa bacteraemia died 5 days after isolation of the organism from her blood. The two patients with C. albicans bacteraemia had totally implantable venous access systems (TIVAS) in situ and both recovered following appropriate therapy. These observations suggest that bacteraemia is rare in patients with CF but that there is a significant risk of fungaemia in a susceptible minority. The implications of these findings, as they relate to management of infections and care of indwelling catheters in such patients, are discussed.
Introduction Despite a persistent bacterial load, bacteraemia from lung disease is rarely reported in patients with cystic fibrosis (CF). Pseudomonas aeruginosa and Staphylococcus aureus are c o m m o n l y isolated from the s p u t u m of adults with C F , yet bacteraemia involving these organisms is extremely rare. We have previously reported one case of P. aeruginosa bacteraemia in a y o u n g m a n with C F 1 and there has been one report of S. aureus bacteraemia in an infant with CF. z Presently, figures are not available for the incidence of bacteraemia in C F patients with acute exacerbations of their p u l m o n a r y disease. T h e recent trend toward h o m e t r e a t m e n t with intravenous antibiotics in the m a n a g e m e n t of these acute p u l m o n a r y exacerbations had led to the use of totally implantable venous access systems ( T I V A S ) ? -~ T h e s e devices m i g h t be expected to be associated with a higher risk of bacteraemia or fungaemia and indeed there is one report of C. albicans fungaemia complicating the use of a P o r t - a - C a t h system. 4 W e present the results of a prospective study on bacteraemia and fungaemia during p u l m o n a r y infective exacerbations in adults with C F and report on the influence of T I V A S on this incidence. * Address correspondence to: Dr John V. Fahy, Box oi3o, U C S F Medical Center, 505 Parnassus Avenue, San Francisco, CA 94143, U.S.A. oi63-4453/92/o3o24I +05 $03.oo/o
© I99I T h e British Society for the Study of Infection
242
J.v. FAHY ET AL. Materials and methods
Patients
Fifty consecutive admissions (involving 29 patients) to an adult CF centre for management of infective exacerbations of pulmonary disease were studied. On admission, patients described typical features of a lower respiratory tract infection with malaise, cough producing increasing amounts of purulent sputum and with dyspnoea. T h e mean age of the patients was 23 years (range I4-4I years). T h e sputum of 26 patients was colonised with P. aeruginosa and three had sputum colonised with P. cepacia. All patients had records of prior colonisation of sputum with S. aureus but only six patients (20 %) had S. aureus isolated from their sputum during the study. Eight patients (28 %) had indwelling subcutaneous venous access systems in situ. Seven of these had a T I V A S (Chem O Port or Port-a-Cath) while another had a tunnelled central catheter (Hickmann). Blood cultures
Body temperature was recorded on admission and thereafter 4 hourly if the patient was febrile and i2 hourly if afebrile. Patients febrile (temperature > 37 °C) on admission or who became febrile during treatment had blood drawn by means of a strictly aseptic technique for paired aerobic and anaerobic bacterial culture as well as fungal culture. T h e following blood culture systems were used: Signal bottle (Oxoid Ltd, Basingstoke, U.K.) for aerobic and anaerobic bacteria, Bactec 6B bottle (Johnson Labs Inc, U.S.A.) for radiometric determination of aerobic bacteria and Myocult bottle (Medical Wire and Equipment Co., Corsham, U.K.) for fungi and clinically important yeasts (a Casteneda-type bottle). T h e Signal and Bactec blood cultures were kept for 7 days and examined/tested for growth twice daily for the first 2 days and thereafter daily. T h e fungal blood cultures were kept for 3 weeks and examined daily for growth. Results
Fifty consecutive admissions comprised 29 different patients who spent I393 bed days in hospital. Of these patients, 18 (62 %) developed 86 febrile episodes, while II patients (38 %) did not experience any fever at all. One patient had been in hospital for 3oo days while awaiting heart-lung transplantation and accounted for 29 febrile episodes. Another patient developed P. aeruginosa bacteraemia and two others developed C. albicans fungaemia. This represented an overall incidence of positive blood cultures in febrile patients of 3"5 % (95 % C.I., 2 - i i %). T h e incidence of bacteraemia in febrile patients was 1.2% (95 % C.I., I-6 %) and the incidence of fungaemia in such patients was 2"3 % (95 % C.I., I'5-8 %). Pseudomonas aeruginosa b a c t e r a e m i a Pseudomonas aeruginosa was isolated from both Signal and Bactec bottles after 48 hours' incubation. Final identification was achieved with the API 2oE (API Ltd, France) bacterial identification system. The patient was a young woman aged I8 years who was critically ill at the time she developed bacteraemia.
Bacteraemia and fungaemia with cystic fibrosis
243
Mechanical ventilation for overwhelming pulmonary infection and respiratory failure had been complicated by a tension pneumothorax requiring chest tube drainage. She also had a history of hepatic failure, portal hypertension, and bleeding oesophageal varices which had required emergency surgery and creation of a mesocaval shunt 6 months previously. T h e r e was evidence of mild hypersplenism and of recent infection with cytomegalovirus (CMV). She was not deficient in immunoglobulin. T w o days earlier, fibreoptic bronchoscopy had been performed because of diffuse pulmonary infiltrates seen on chest X-ray and a suspicion of CMV pneumonitis (bronchial washings only were taken; a biopsy was not done). Dopamine in low dosage was being administered for diminished urine output (blood pressure remained stable at I4o/8o). T h e strain of P. aeruginosa in her blood had the same antimicrobial sensitivity as that in her sputum. During the course of this study she had 13 negative blood culture sets before she developed P. aeruginosa bacteraemia. She died 5 days after the strains had been identified. Candida albicans fungaemia
T w o patients, both of whom had a T I V A S in situ, developed C. albicans fungaemia. In each case high fever and rigors developed while the patient was being treated with intravenous broad-spectrum antibiotics for infective exacerbations of pulmonary disease. (Both patients required protracted courses, 4 weeks of continuous antibiotic therapy having been given in one case, z2 weeks in the other.) T h e r e was a history in each case of long-term corticosteroid treatment and both patients had received booster steroid treatment during the same period in hospital. One patient had insulindependent diabetes mellitus, the other impaired glucose tolerance. Transient hypotension developed in one patient only and resolved without the need for inotropic support. Management of the C. albicans fungaemia consisted of removal of the T I V A S and administration of intravenous amphotericin B to a total dose of I g. Recovery was complete in each case. Echocardiography was performed on both patients but did not show any evidence of valvular vegetations. In one patient, a tunnelled central catheter was placed 2 months later without further complications. It is of interest that of the other six patients with a T I V A S , and who did not develop C. albicans fungaemia, one had insulin-dependent diabetes mellitus but the other five had normal glucose tolerance.
Discussion This is the first prospective study to report on the incidence of bacteraemia and fungaemia in adult patients with CF who are in hospital with acute exacerbations of pulmonary disease. Only one episode of P. aeruginosa bacteraemia was identified from a total of 86 sets of blood cultures taken from febrile patients. This rarity of bacterial sepsis in CF may relate to potent humoral and cellular defence mechanisms in response to chronic pulmonary suppuration. Increased bactericidal activity against P. aeruginosa has not been demonstrated in patients with CF but the protective effect of antibodies to P. aeruginosa in this context may have been to promote type-specific phagocytosis by neutrophils or macrophages. 7 Recent studies of reticuloendothelial
244
J . v . FAHY E T A L .
clearance in CF have demonstrated enhanced clearance of immune complexes 8 and this too may contribute to the inhibition of bacteraemia. T h e case of P. aeruginosa bacteraemia presented here is to our knowledge only the second reported case in an adult with CF. In this case, isolation of P. aeruginosa from the blood was a preterminal event in a patient with grossly impaired host defence mechanisms. T h e identification of two cases of C. albicans fungaemia in this group raises important questions regarding the use of T I V A S in CF patients. T h e procedure has become an accepted form of management for those patients who require frequent courses of intravenous antibiotics and who have poor peripheral venous access. 3-6 In general, there has been a very low incidence of infection associated with the use of T I V A S in CF patients according to published reviews. Stead et al., 4 reported one case of systemic candidiasis associated with use of a T I V A S in an adult with CF. Essex-Cater found one case of local infection of the skin overlying the T I V A S site and removed the system from one CF patient because of the clinical suspicion of infection (not bacteriologically confirmed) among I I children with CF and T I V A S in situ. Cassey et al., ~ reviewed the use of T I V A S in I3 children with CF and did not find any case of line-associated sepsis. Thus, the rate of systemic candidiasis reported here (two of eight patients with indwelling catheters becoming infected) is high. Undoubtedly the combination of diabetes mellitus, corticosteroid therapy, and the need for extended courses of broadspectrum antibiotics, contributed significantly by encouraging endogenous fungal overgrowth and subsequent catheter colonisation. Two of the three patients with the combination of an indwelling venous access device and impaired glucose tolerance developed C. albicans fungaemia while receiving broad-spectrum antibiotic therapy. Both patients who developed C. albicans fungaemia were also receiving corticosteroids and it is worth noting that, in the only previous report of systemic candidiasis complicating the use of T I V A S in a CF patient, corticosteroids were also being given at the same time. 4 Many CF patients have the predispositions described above for developing local candidiasis, predispositions which in association with the use of T I V A S place them at increased risk of systemic candidiasis. It would now seem desirable to consider potential prophylactic measures in order to prevent fungal colonisation of T I V A S in CF patients, especially in those with impaired glucose tolerance or who require corticosteroids. T h e r e are no published reviews regarding such measures in CF patients but fungal prophylaxis in other patients has been recommended. Brennan et al., 9 used a dilute solution of amphotericin to flush the central catheters of I2 patients requiring long-term parenteral nutrition. Used prophylactically twice a week, this measure prevented any episode of systemic candidiasis. T h e same investigators noted that four of 28 patients requiring total parenteral nutrition had previously developed C. albicans sepsis when prophylactic measures had not been taken. Since that study was reported in I972, however, routine flushing of central lines with amphotericin has not gained wide acceptance. More recently, Lucht et al., 1° reported that oral ketoconazole or fluconazole prevented any episode of systemic candidiasis in 25 patients who required prolonged courses of antibiotics through T I V A S for treatment of chronic infections caused by Gram-negative bacteria. Thus, fluconazole (being less
Bacteraemia and f u n g a e m i a with cystic fibrosis
245
h e p a t o x i c t h a n k e t o c o n a z o l e ) m a y p r o v e u s e f u l f o r f u n g a l p r o p h y l a x i s in C F p a t i e n t s w i t h a T I V A S in situ. F i n a l l y , w e c a n i n f e r f r o m t h e r e s u l t s o f this s t u d y t h a t P. aeruginosa or S. aureus b a c t e r a e m i a is r a r e in a d u l t C F p a t i e n t s w i t h a c u t e e x a c e r b a t i o n s o f t h e i r p u l m o n a r y disease a n d t h e r e f o r e t h a t r o u t i n e c u l t u r e s o f b l o o d f r o m s u c h f e b r i l e p a t i e n t s is u n n e c e s s a r y . S h o u l d f e v e r p e r s i s t , h o w e v e r , d u r i n g t h e r a p y , a n d if a T I V A S is in situ, t h e n b l o o d f o r c u l t u r e s h o u l d b e t a k e n in o r d e r to exclude systemic candidiasis. (This work was supported in part by a grant f r o m the Cystic Fibrosis Association of Ireland.) References
I. Coffey MJ, Keoghan MT, FitzGerald MX. Pseudomonas aeruginosa septicaemia in a young adult with CF. Respir Med 199o; 84: 167-168. 2. McCarthy MM, Rourke MM, Spock A. Bacteraemia in patients with CF. Clin Paediatr 198o; I9:746-748. 3- Pattison J, HeafDP. Totally implantable vascular access in treatment of CF. Lancet I986; i: 799. 4- Stead RJ, Davison T I , Duncan FR, Hodson ME, Barren JC. Use of totally implantable system for venous access in CF. Thorax I987; 4z: I49-I5O. 5- Cassey J, Ford WDA, O'Brien L, Martin AJ. Totally implantable system for venous access in children. Clin Paediatr I988; z7: 91-95. 6. Essex-Cater A, Gilbert J, Robinson T, Littlewood JM. Totally implantable venous access systems in a paediatric practice. Arch Dis Child I989; 64: I I9-I23. 7. Hoiby N, Oiling S. Pseudomonas aeruginosa infection in cystic fibrosis. Acta Pathol Microbiol Scand Sect I977; 85: IO7-I I4. 8. Mantzouranis EC, Rosen FS, Colten HR. Reticuloendothelial clearance in cystic fibrosis and other inflammatory lung diseases. N EnglJ Med 1988; 3x9: 338-343. 9. Brennan MF, Goldman MH, O'Connell RC, Kundsin RB, Moore FB. Prolonged parenteral alimentation: candida growth and the prevention of candidaemia by amphotericin instillation. Ann Surg I972; I76: 265-270. IO. Lucht F, Vergely N, Rousset H, Bousket G, Balique ]'G. Totally implantable vascular access for antimicrobial infusion at home and prevention of systemic candidosis. Lancet 1989; i: 666.
10
JIN22
B a c t e r a e m i a and f u n g a e m i a in adults w i t h cystic fibrosis J. V. Fahy,* M. T. Keoghan, E.J. Crummy and M. X. FitzGerald Adult Cystic Fibrosis Centre, St Vincent's Hospital, Elm Park, Dublin 4, Republic of Ireland Accepted for publication 25 October 299o
Summary The incidence of bacteraemia and fungaemia was determined in 29 adults with cystic fibrosis (CF) during 50 consecutive admissions to hospital for management of infective exacerbations of pulmonary disease. Blood was drawn for aerobic, anaerobic and fungal cultures from all patients who were febrile on admission or who became febrile during treatment. The population included eight patients who had indwelling venous access systems in situ. The overall incidence of positive blood cultures in febrile patients was 3"5 % [95 % confidence interval (C.I.), I-6 %]. We recorded one case of Pseudomonas aeruginosa bacteraemia and two cases of Candida albicans fungaemia. The patient with P. aeruginosa bacteraemia died 5 days after isolation of the organism from her blood. The two patients with C. albicans bacteraemia had totally implantable venous access systems (TIVAS) in situ and both recovered following appropriate therapy. These observations suggest that bacteraemia is rare in patients with CF but that there is a significant risk of fungaemia in a susceptible minority. The implications of these findings, as they relate to management of infections and care of indwelling catheters in such patients, are discussed.
Introduction Despite a persistent bacterial load, bacteraemia from lung disease is rarely reported in patients with cystic fibrosis (CF). Pseudomonas aeruginosa and Staphylococcus aureus are c o m m o n l y isolated from the s p u t u m of adults with C F , yet bacteraemia involving these organisms is extremely rare. We have previously reported one case of P. aeruginosa bacteraemia in a y o u n g m a n with C F 1 and there has been one report of S. aureus bacteraemia in an infant with CF. z Presently, figures are not available for the incidence of bacteraemia in C F patients with acute exacerbations of their p u l m o n a r y disease. T h e recent trend toward h o m e t r e a t m e n t with intravenous antibiotics in the m a n a g e m e n t of these acute p u l m o n a r y exacerbations had led to the use of totally implantable venous access systems ( T I V A S ) ? -~ T h e s e devices m i g h t be expected to be associated with a higher risk of bacteraemia or fungaemia and indeed there is one report of C. albicans fungaemia complicating the use of a P o r t - a - C a t h system. 4 W e present the results of a prospective study on bacteraemia and fungaemia during p u l m o n a r y infective exacerbations in adults with C F and report on the influence of T I V A S on this incidence. * Address correspondence to: Dr John V. Fahy, Box oi3o, U C S F Medical Center, 505 Parnassus Avenue, San Francisco, CA 94143, U.S.A. oi63-4453/92/o3o24I +05 $03.oo/o
© I99I T h e British Society for the Study of Infection
242
J.v. FAHY ET AL. Materials and methods
Patients
Fifty consecutive admissions (involving 29 patients) to an adult CF centre for management of infective exacerbations of pulmonary disease were studied. On admission, patients described typical features of a lower respiratory tract infection with malaise, cough producing increasing amounts of purulent sputum and with dyspnoea. T h e mean age of the patients was 23 years (range I4-4I years). T h e sputum of 26 patients was colonised with P. aeruginosa and three had sputum colonised with P. cepacia. All patients had records of prior colonisation of sputum with S. aureus but only six patients (20 %) had S. aureus isolated from their sputum during the study. Eight patients (28 %) had indwelling subcutaneous venous access systems in situ. Seven of these had a T I V A S (Chem O Port or Port-a-Cath) while another had a tunnelled central catheter (Hickmann). Blood cultures
Body temperature was recorded on admission and thereafter 4 hourly if the patient was febrile and i2 hourly if afebrile. Patients febrile (temperature > 37 °C) on admission or who became febrile during treatment had blood drawn by means of a strictly aseptic technique for paired aerobic and anaerobic bacterial culture as well as fungal culture. T h e following blood culture systems were used: Signal bottle (Oxoid Ltd, Basingstoke, U.K.) for aerobic and anaerobic bacteria, Bactec 6B bottle (Johnson Labs Inc, U.S.A.) for radiometric determination of aerobic bacteria and Myocult bottle (Medical Wire and Equipment Co., Corsham, U.K.) for fungi and clinically important yeasts (a Casteneda-type bottle). T h e Signal and Bactec blood cultures were kept for 7 days and examined/tested for growth twice daily for the first 2 days and thereafter daily. T h e fungal blood cultures were kept for 3 weeks and examined daily for growth. Results
Fifty consecutive admissions comprised 29 different patients who spent I393 bed days in hospital. Of these patients, 18 (62 %) developed 86 febrile episodes, while II patients (38 %) did not experience any fever at all. One patient had been in hospital for 3oo days while awaiting heart-lung transplantation and accounted for 29 febrile episodes. Another patient developed P. aeruginosa bacteraemia and two others developed C. albicans fungaemia. This represented an overall incidence of positive blood cultures in febrile patients of 3"5 % (95 % C.I., 2 - i i %). T h e incidence of bacteraemia in febrile patients was 1.2% (95 % C.I., I-6 %) and the incidence of fungaemia in such patients was 2"3 % (95 % C.I., I'5-8 %). Pseudomonas aeruginosa b a c t e r a e m i a Pseudomonas aeruginosa was isolated from both Signal and Bactec bottles after 48 hours' incubation. Final identification was achieved with the API 2oE (API Ltd, France) bacterial identification system. The patient was a young woman aged I8 years who was critically ill at the time she developed bacteraemia.
Bacteraemia and fungaemia with cystic fibrosis
243
Mechanical ventilation for overwhelming pulmonary infection and respiratory failure had been complicated by a tension pneumothorax requiring chest tube drainage. She also had a history of hepatic failure, portal hypertension, and bleeding oesophageal varices which had required emergency surgery and creation of a mesocaval shunt 6 months previously. T h e r e was evidence of mild hypersplenism and of recent infection with cytomegalovirus (CMV). She was not deficient in immunoglobulin. T w o days earlier, fibreoptic bronchoscopy had been performed because of diffuse pulmonary infiltrates seen on chest X-ray and a suspicion of CMV pneumonitis (bronchial washings only were taken; a biopsy was not done). Dopamine in low dosage was being administered for diminished urine output (blood pressure remained stable at I4o/8o). T h e strain of P. aeruginosa in her blood had the same antimicrobial sensitivity as that in her sputum. During the course of this study she had 13 negative blood culture sets before she developed P. aeruginosa bacteraemia. She died 5 days after the strains had been identified. Candida albicans fungaemia
T w o patients, both of whom had a T I V A S in situ, developed C. albicans fungaemia. In each case high fever and rigors developed while the patient was being treated with intravenous broad-spectrum antibiotics for infective exacerbations of pulmonary disease. (Both patients required protracted courses, 4 weeks of continuous antibiotic therapy having been given in one case, z2 weeks in the other.) T h e r e was a history in each case of long-term corticosteroid treatment and both patients had received booster steroid treatment during the same period in hospital. One patient had insulindependent diabetes mellitus, the other impaired glucose tolerance. Transient hypotension developed in one patient only and resolved without the need for inotropic support. Management of the C. albicans fungaemia consisted of removal of the T I V A S and administration of intravenous amphotericin B to a total dose of I g. Recovery was complete in each case. Echocardiography was performed on both patients but did not show any evidence of valvular vegetations. In one patient, a tunnelled central catheter was placed 2 months later without further complications. It is of interest that of the other six patients with a T I V A S , and who did not develop C. albicans fungaemia, one had insulin-dependent diabetes mellitus but the other five had normal glucose tolerance.
Discussion This is the first prospective study to report on the incidence of bacteraemia and fungaemia in adult patients with CF who are in hospital with acute exacerbations of pulmonary disease. Only one episode of P. aeruginosa bacteraemia was identified from a total of 86 sets of blood cultures taken from febrile patients. This rarity of bacterial sepsis in CF may relate to potent humoral and cellular defence mechanisms in response to chronic pulmonary suppuration. Increased bactericidal activity against P. aeruginosa has not been demonstrated in patients with CF but the protective effect of antibodies to P. aeruginosa in this context may have been to promote type-specific phagocytosis by neutrophils or macrophages. 7 Recent studies of reticuloendothelial
244
J . v . FAHY E T A L .
clearance in CF have demonstrated enhanced clearance of immune complexes 8 and this too may contribute to the inhibition of bacteraemia. T h e case of P. aeruginosa bacteraemia presented here is to our knowledge only the second reported case in an adult with CF. In this case, isolation of P. aeruginosa from the blood was a preterminal event in a patient with grossly impaired host defence mechanisms. T h e identification of two cases of C. albicans fungaemia in this group raises important questions regarding the use of T I V A S in CF patients. T h e procedure has become an accepted form of management for those patients who require frequent courses of intravenous antibiotics and who have poor peripheral venous access. 3-6 In general, there has been a very low incidence of infection associated with the use of T I V A S in CF patients according to published reviews. Stead et al., 4 reported one case of systemic candidiasis associated with use of a T I V A S in an adult with CF. Essex-Cater found one case of local infection of the skin overlying the T I V A S site and removed the system from one CF patient because of the clinical suspicion of infection (not bacteriologically confirmed) among I I children with CF and T I V A S in situ. Cassey et al., ~ reviewed the use of T I V A S in I3 children with CF and did not find any case of line-associated sepsis. Thus, the rate of systemic candidiasis reported here (two of eight patients with indwelling catheters becoming infected) is high. Undoubtedly the combination of diabetes mellitus, corticosteroid therapy, and the need for extended courses of broadspectrum antibiotics, contributed significantly by encouraging endogenous fungal overgrowth and subsequent catheter colonisation. Two of the three patients with the combination of an indwelling venous access device and impaired glucose tolerance developed C. albicans fungaemia while receiving broad-spectrum antibiotic therapy. Both patients who developed C. albicans fungaemia were also receiving corticosteroids and it is worth noting that, in the only previous report of systemic candidiasis complicating the use of T I V A S in a CF patient, corticosteroids were also being given at the same time. 4 Many CF patients have the predispositions described above for developing local candidiasis, predispositions which in association with the use of T I V A S place them at increased risk of systemic candidiasis. It would now seem desirable to consider potential prophylactic measures in order to prevent fungal colonisation of T I V A S in CF patients, especially in those with impaired glucose tolerance or who require corticosteroids. T h e r e are no published reviews regarding such measures in CF patients but fungal prophylaxis in other patients has been recommended. Brennan et al., 9 used a dilute solution of amphotericin to flush the central catheters of I2 patients requiring long-term parenteral nutrition. Used prophylactically twice a week, this measure prevented any episode of systemic candidiasis. T h e same investigators noted that four of 28 patients requiring total parenteral nutrition had previously developed C. albicans sepsis when prophylactic measures had not been taken. Since that study was reported in I972, however, routine flushing of central lines with amphotericin has not gained wide acceptance. More recently, Lucht et al., 1° reported that oral ketoconazole or fluconazole prevented any episode of systemic candidiasis in 25 patients who required prolonged courses of antibiotics through T I V A S for treatment of chronic infections caused by Gram-negative bacteria. Thus, fluconazole (being less
Bacteraemia and f u n g a e m i a with cystic fibrosis
245
h e p a t o x i c t h a n k e t o c o n a z o l e ) m a y p r o v e u s e f u l f o r f u n g a l p r o p h y l a x i s in C F p a t i e n t s w i t h a T I V A S in situ. F i n a l l y , w e c a n i n f e r f r o m t h e r e s u l t s o f this s t u d y t h a t P. aeruginosa or S. aureus b a c t e r a e m i a is r a r e in a d u l t C F p a t i e n t s w i t h a c u t e e x a c e r b a t i o n s o f t h e i r p u l m o n a r y disease a n d t h e r e f o r e t h a t r o u t i n e c u l t u r e s o f b l o o d f r o m s u c h f e b r i l e p a t i e n t s is u n n e c e s s a r y . S h o u l d f e v e r p e r s i s t , h o w e v e r , d u r i n g t h e r a p y , a n d if a T I V A S is in situ, t h e n b l o o d f o r c u l t u r e s h o u l d b e t a k e n in o r d e r to exclude systemic candidiasis. (This work was supported in part by a grant f r o m the Cystic Fibrosis Association of Ireland.) References
I. Coffey MJ, Keoghan MT, FitzGerald MX. Pseudomonas aeruginosa septicaemia in a young adult with CF. Respir Med 199o; 84: 167-168. 2. McCarthy MM, Rourke MM, Spock A. Bacteraemia in patients with CF. Clin Paediatr 198o; I9:746-748. 3- Pattison J, HeafDP. Totally implantable vascular access in treatment of CF. Lancet I986; i: 799. 4- Stead RJ, Davison T I , Duncan FR, Hodson ME, Barren JC. Use of totally implantable system for venous access in CF. Thorax I987; 4z: I49-I5O. 5- Cassey J, Ford WDA, O'Brien L, Martin AJ. Totally implantable system for venous access in children. Clin Paediatr I988; z7: 91-95. 6. Essex-Cater A, Gilbert J, Robinson T, Littlewood JM. Totally implantable venous access systems in a paediatric practice. Arch Dis Child I989; 64: I I9-I23. 7. Hoiby N, Oiling S. Pseudomonas aeruginosa infection in cystic fibrosis. Acta Pathol Microbiol Scand Sect I977; 85: IO7-I I4. 8. Mantzouranis EC, Rosen FS, Colten HR. Reticuloendothelial clearance in cystic fibrosis and other inflammatory lung diseases. N EnglJ Med 1988; 3x9: 338-343. 9. Brennan MF, Goldman MH, O'Connell RC, Kundsin RB, Moore FB. Prolonged parenteral alimentation: candida growth and the prevention of candidaemia by amphotericin instillation. Ann Surg I972; I76: 265-270. IO. Lucht F, Vergely N, Rousset H, Bousket G, Balique ]'G. Totally implantable vascular access for antimicrobial infusion at home and prevention of systemic candidosis. Lancet 1989; i: 666.
10
JIN22
