Scot. moo. J., 1976, 21: 73
TREATMENT OF FEBRILE EPISODES IN NEUTROPENIC PATIENTS V. Melikian and R. Falk Department of Medicine, Dudley Road Hospital, Birmingham
F A I L U R E to diagnose infection in neutropenic patients is a major cause of morbidity and mortality-hence the empirical use of antibiotics in those in whom bacterial infection is suspected (Tattersall et al., 1972). Tobramycin is a relatively new aminoglycoside antibiotic with a greater action against Pseudomonas species than gentamicin, but with a similar antibacterial spectrum (Geddes et al., 1974). In this study experience with tobramycin in combination with clindamycin, and in a few cases with co-trimoxazole, for the treatment of febrile episodes in neutropenic or immuno-suppressed patients is described.
improvement and resolution of the pyrexia and, in addition, in proven infections by the eradication of organisms from relevant cultures. Daily full blood counts were carried out in all patients and regular estimations of blood urea, electrolytes and creatinine; urine deposit examination for casts and R.B.C., and audiometry performed to assess ototoxicity. Of the 25 febrile episodes studied in 14 patients, 12 were due to proven infection, 9 were classified as probable and 4 as unlikely. Details of patients with proven infection are shown in Tables I and II. Ten patients have so far died in this study and in no case could death be attributed to bacterial infection. The causes of death were bleeding diathesis of underlying disease (7) and Candida septicaemia (3). Of the patients who had audiometric testing there was no deterioration in hearing, with the exception of one who had three courses of tobramycin and had previously received gentamicin. In one case transient rise of blood urea during therapy was noted. In the remaining patients there was no evidence of nephrotoxicity. To date, tobramycin has been administered as a single intravenous bolus injection in more than one thousand instances without any side effects.
Clinical results Twenty-five febrile episodes were treated in a total of 14 patients. Eleven patients had acute myeloid leukaemia; one had blast-metamorphosis in chronic granulocytic leukaemia; one, chronic lymphatic leukaemia and one, malignant lymphoma. Antibiotic therapy was commenced if patients developed a temperature greater than 38°C. on 2 consecutive 4-hourly readings in the absence of an obvious non-bacterial cause. Physical examination was performed to detect any source of infection and blood cultures, MSU and chest X-ray were taken. In addition swabs were taken from nose, Conclusion throat, axillae and perineum. In contrast to other series, the incidence of Tobramycin was administered as an intra- septicaemia in the proven infection group is venous bolus dose, initially at 80 mg. 8-hourly low. One may postulate that the prompt use or 3 mg. per kg. per 24 hours, increasing of antibiotics in hospital patients prevented to 4.5 mg. per kg. daily in 3 divided doses if the progression of infection to septicaemia. necessary. Clindamycin was given orally 150 Unlike some previous series (Klastersky et mg. 4 times daily. If there was no sign of al., 1974) most of our patients were neutroimprovement, co-trimoxazole was added, 2 penic. It is often said that gentamicin is tablets twice daily. relatively ineffective in neutropenic patients Serum levels of tobramycin were measured (Klastersky et al., 1974; Levine et aI., 1974) immediately before an intravenous dose and and this is the rationale for the addition of half-an-hour afterwards, on the second day of carbenicillin to antibiotic combinations where treatment and after a change in dosage. Pseudomonas infection is feared. We did not Successful treatment was measured by clinical find evidence that our combination was
Melikian and Falk
Table I. Details of proven bacterial infections with septicaemia. Patient
Disease
Organism
F.B.
Acute myeloid leukaemia
Klebsiella sp,
650
R
F.L.
Acute myeloid leukaemia
E. coli Strep. pneumoniae Enterobacter sp,
240
R
Neutrophils per mm"
Outcome R=recovery
F.L.
Acute myeloid leukaemia
E. coli Klebsiella sp.
900
R
F.L.
Acute myeloid leukaemia
E. coli
230
R
A.S.
Malignant lymphoma
Serratia marcescens
M.P.
Chronic lymphatic leukaemia
Proteus mirabilis
2500
Died
500
R
Table II.Details of proven bacterial infections without septicaemia. Patient
Disease
Infection
Organism
D.B.
Acute myeloid leukaemia
Infected LV. drip site ? septicaemia
Acinetobacter anitratus Staph. aureus
1000
R
L.G.
Acute myeloid leukaemia
Otitis media Jaw abscess
Strep. pyogenes
2200
R
D.P.
Acute myeloid leukaemia
Throat infection
Strep. pyogenes
1800
R
E.B.
Acute myeloid leukaemia
Pneumonia
Pseudomonas aeruginosa
360
R
G.K.
Chronic granulocytic leukaemia Blast transformation
Pneumonia
Staph. albus
4300
R
E.B.
Acute myeloid leukaemia
Throat infection
Staph. albus
1000
Died
Neutrophils Outcome R=Recovery per mm"
ineffective despite severe neutropenia in some Klastersky, J., Henri, A., Hensgens, C., Daneau, Do. (1974). Gram-negative infections in cancer. Journal patients. That tobramycin is more effective of the American Medical Association, 227, 45 than gentamicin in the neutropenic patient Levine, A. S., Schimpft', S. C., Graw, R. G., Young, R. has not been proven, but this finding suggests C. (1974). Haernatologic malignancies and marrow failure states: progress in the management of comthat it may be. REFERENCES
Geddes, A. M., Goodall, J. A. D., Speirs, C. F., Gillett, A. P., Andrews, J., Williams, J. D. (1974). Clinical and laboratory studies with tobramycin. Chemotherapy, 20, 245
74
plicating infections. Seminars in Haematology, 2, 141 Tattersall, M. H. N., Speirs, A. S. D., Darrell, J. H. (1972). Initial therapy with combination of five antibiotics in febrile patients with leukaemia and neutropenia. Lancet, 1, 162
TREATMENT OF FEBRILE EPISODES IN NEUTROPENIC PATIENTS V. Melikian and R. Falk Department of Medicine, Dudley Road Hospital, Birmingham
F A I L U R E to diagnose infection in neutropenic patients is a major cause of morbidity and mortality-hence the empirical use of antibiotics in those in whom bacterial infection is suspected (Tattersall et al., 1972). Tobramycin is a relatively new aminoglycoside antibiotic with a greater action against Pseudomonas species than gentamicin, but with a similar antibacterial spectrum (Geddes et al., 1974). In this study experience with tobramycin in combination with clindamycin, and in a few cases with co-trimoxazole, for the treatment of febrile episodes in neutropenic or immuno-suppressed patients is described.
improvement and resolution of the pyrexia and, in addition, in proven infections by the eradication of organisms from relevant cultures. Daily full blood counts were carried out in all patients and regular estimations of blood urea, electrolytes and creatinine; urine deposit examination for casts and R.B.C., and audiometry performed to assess ototoxicity. Of the 25 febrile episodes studied in 14 patients, 12 were due to proven infection, 9 were classified as probable and 4 as unlikely. Details of patients with proven infection are shown in Tables I and II. Ten patients have so far died in this study and in no case could death be attributed to bacterial infection. The causes of death were bleeding diathesis of underlying disease (7) and Candida septicaemia (3). Of the patients who had audiometric testing there was no deterioration in hearing, with the exception of one who had three courses of tobramycin and had previously received gentamicin. In one case transient rise of blood urea during therapy was noted. In the remaining patients there was no evidence of nephrotoxicity. To date, tobramycin has been administered as a single intravenous bolus injection in more than one thousand instances without any side effects.
Clinical results Twenty-five febrile episodes were treated in a total of 14 patients. Eleven patients had acute myeloid leukaemia; one had blast-metamorphosis in chronic granulocytic leukaemia; one, chronic lymphatic leukaemia and one, malignant lymphoma. Antibiotic therapy was commenced if patients developed a temperature greater than 38°C. on 2 consecutive 4-hourly readings in the absence of an obvious non-bacterial cause. Physical examination was performed to detect any source of infection and blood cultures, MSU and chest X-ray were taken. In addition swabs were taken from nose, Conclusion throat, axillae and perineum. In contrast to other series, the incidence of Tobramycin was administered as an intra- septicaemia in the proven infection group is venous bolus dose, initially at 80 mg. 8-hourly low. One may postulate that the prompt use or 3 mg. per kg. per 24 hours, increasing of antibiotics in hospital patients prevented to 4.5 mg. per kg. daily in 3 divided doses if the progression of infection to septicaemia. necessary. Clindamycin was given orally 150 Unlike some previous series (Klastersky et mg. 4 times daily. If there was no sign of al., 1974) most of our patients were neutroimprovement, co-trimoxazole was added, 2 penic. It is often said that gentamicin is tablets twice daily. relatively ineffective in neutropenic patients Serum levels of tobramycin were measured (Klastersky et al., 1974; Levine et aI., 1974) immediately before an intravenous dose and and this is the rationale for the addition of half-an-hour afterwards, on the second day of carbenicillin to antibiotic combinations where treatment and after a change in dosage. Pseudomonas infection is feared. We did not Successful treatment was measured by clinical find evidence that our combination was
Melikian and Falk
Table I. Details of proven bacterial infections with septicaemia. Patient
Disease
Organism
F.B.
Acute myeloid leukaemia
Klebsiella sp,
650
R
F.L.
Acute myeloid leukaemia
E. coli Strep. pneumoniae Enterobacter sp,
240
R
Neutrophils per mm"
Outcome R=recovery
F.L.
Acute myeloid leukaemia
E. coli Klebsiella sp.
900
R
F.L.
Acute myeloid leukaemia
E. coli
230
R
A.S.
Malignant lymphoma
Serratia marcescens
M.P.
Chronic lymphatic leukaemia
Proteus mirabilis
2500
Died
500
R
Table II.Details of proven bacterial infections without septicaemia. Patient
Disease
Infection
Organism
D.B.
Acute myeloid leukaemia
Infected LV. drip site ? septicaemia
Acinetobacter anitratus Staph. aureus
1000
R
L.G.
Acute myeloid leukaemia
Otitis media Jaw abscess
Strep. pyogenes
2200
R
D.P.
Acute myeloid leukaemia
Throat infection
Strep. pyogenes
1800
R
E.B.
Acute myeloid leukaemia
Pneumonia
Pseudomonas aeruginosa
360
R
G.K.
Chronic granulocytic leukaemia Blast transformation
Pneumonia
Staph. albus
4300
R
E.B.
Acute myeloid leukaemia
Throat infection
Staph. albus
1000
Died
Neutrophils Outcome R=Recovery per mm"
ineffective despite severe neutropenia in some Klastersky, J., Henri, A., Hensgens, C., Daneau, Do. (1974). Gram-negative infections in cancer. Journal patients. That tobramycin is more effective of the American Medical Association, 227, 45 than gentamicin in the neutropenic patient Levine, A. S., Schimpft', S. C., Graw, R. G., Young, R. has not been proven, but this finding suggests C. (1974). Haernatologic malignancies and marrow failure states: progress in the management of comthat it may be. REFERENCES
Geddes, A. M., Goodall, J. A. D., Speirs, C. F., Gillett, A. P., Andrews, J., Williams, J. D. (1974). Clinical and laboratory studies with tobramycin. Chemotherapy, 20, 245
74
plicating infections. Seminars in Haematology, 2, 141 Tattersall, M. H. N., Speirs, A. S. D., Darrell, J. H. (1972). Initial therapy with combination of five antibiotics in febrile patients with leukaemia and neutropenia. Lancet, 1, 162
