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Teicoplanin in the treatment of infection caused by Gram-positive organisms
Journal
of Hospital
Infection
Teicoplanin
(1986) 7 (Supplement
in the treatment Gram-positive
A. H. Williams, Department
R. N. Griineberg,
A), 101-l 03
of infection organisms A. Webster
of Microbiology, University London WClE 6AU
caused
by
and G. L. Ridgway
College Hospital,
Summary: Teicoplanin was used to treat 94 hospital in-patients of confirmed or presumed Gram-positive infections over a period of 12 months. Eighty-five patients were subsequently found to be evaluable; 31 had soft tissue infections, 10 endocarditis, 8 urinary tract infections, 12 septicaemias, 2 chest infections, 7 osteomyelitis or septic arthritis, and 15 were immunosuppressed patients with infected Hickman line site infections. The cure rate of the 85 evaluable episodes was 90% (76 cured). Teicoplanin was well tolerated intravenously and intramuscularly. Adverse reactions occurred in five patients. One patient suffered high tone hearing loss, two patients suffered transient rash, one developed a drug fever and one patient who had concomitant gentamicin developed vestibular damage. It is concluded that teicoplanin is a relatively safe and effacacious treatment for Gram-positive infection. Introduction
Teicoplanin is a new glycopeptide antibiotic produced from the fermentation products of Actinoplanes teichomyceticus. It is a bactericidal antibiotic interfering with cell wall synthesis ‘in a manner similar to Unlike vancomycin, it has a long half-life of the order of vancomycin. 70-lOOh, can be given by fast iv injection or by im injection and is slightly more active than vancomycin in vitro. These properties make it an attractive alternative to vancomycin therapy. The aim of this study was to ascertain the safety and efficacy of teicoplanin in the treatment of Gram-positive infection. Methods
Over a period of 12 months 94 hospital in-patients with confirmed or presumed infections caused by Gram-positive organisms were treated. The drug was given, whenever practicable, as a loading dose of 400mg intravenously followed by daily im or iv doses of 200mg for periods ranging from 1 to 61 days. Of the 85 evaluable patients 31 had soft tissue infections, 10 endocarditis, 8 urinary tract infections; there were 12 septicaemias, 2 chest infections, 7 patients with osteomyelitis or septic arthritis and 15 immunosuppressed patients with infected Hickman line site infections. 01954701/86/07A101+03
0 1986 The Hospital
SO3 00/O
101
Infection
Society
A. H. Williams
et al.
Results
The clinical evaluation of the 85 evaluable patients is shown in Table I. Nine courses of treatment could not be evaluated because of protocol violation, adverse events or death from concurrent disease. The clinical cure rates among the 85 evaluable episodes were: 100% for soft tissue infections, urinary tract infections, chest infections, septicaemia and osteomyelitis, and 70% for endocarditis. The outcome was satisfactory in 61% of the evaluable Hickman line site infections. The overall success rate was 90% of the 85 evaluable treatments. Intramuscular injection was well tolerated. Adverse reactions were noted in five patients (5%) taking the form of transient rash in three patients, fever after the first injection in one patient [possibly related to a concurrent urinary tract infection (UTI)] and high tone (8 kHz) hearing loss in one patient. Table II shows the organisms isolated. Table Type
I. Clinical evaluation of 94 courses of treatment Evaluation
of infection
Soft tissue infections Endocarditis Urinary tract infection Septicaemia Chest infection Osteomyelitis Hickman line site infections
Cure Cure Cure Cure Cure Cure Line retained
No./total 31131 7110
818 12112
212 717 11/15
Overall 85 evaluable episodes treated with 76 cures (90% cures). Nine cases were not evaluable; two with chest infections because of intercurrent Gram-negative septicaemia in one patient and unrelated death after only two doses in the other; three with soft tissue infections and two cases of septicaemia because of protocol violations; one Hickman line site infection because of supervening fatal Gram-negative infection; and one Hickman line site infection due to death from graft versus host disease.
Discussion
Among the 51 patients with soft tissue infections, septicaemia, UTI, chest infections or osteomyelitis, no failures of treatment were seen. Ten patients were treated for endocarditis, five on prosthetic valves. Four of the five episodes of primary endocarditis and three of the five episodes of prosthetic valve endocarditis were cured (one was difficult to evaluate due to the withdrawal of treatment on day 17 due to a drug fever). Five patients were treated with teicoplanin alone (three cures) and in the others teicoplanin was combined with other antibiotics (two with gentamicin, one with flucloxacillin, one with gentamicin plus rifampicin and one with rifampicin), with three cures out of five.
Teicoplanin Table
II.
in Gram-positive
Organisms
Total
on evaluable
aureus
103
cases
Eradication and marked reduction
Organism Methicillin-sensitive Staphylococcus Methicillin-resistant Staph. aureus Streptococcus haemolyticus: group A group G group B Str. faecalis Str. milleri Clostridium perfringens Coagulase-negative staphylococci Str. mitior Str. sanguis Str. bovis Micrococcus
isolated
infections
13 12 9 3 2 9 1 1 15 1 1 1
Persistence 1
6
1 68
8
The difficulty of treating infections, whether endocarditis or Hickman line associated, in the presence of foreign bodies is well recognized. The treatment outcome in these patients seem remarkably good. One patient with a coagulase-negative staphylococcal infection of a ventriculo-atria1 shunt was also treated successfully. We are grateful to the Merrell Dow Research Institute for financial support and to Dr Peter Southgate for advice and encouragement. Our colleagues Dr Alison Webster and Dr Peter Wilson have given much help with this continuing study. We are grateful to many clinical colleagues for permission to treat and report on their patients.
of Hospital
Infection
Teicoplanin
(1986) 7 (Supplement
in the treatment Gram-positive
A. H. Williams, Department
R. N. Griineberg,
A), 101-l 03
of infection organisms A. Webster
of Microbiology, University London WClE 6AU
caused
by
and G. L. Ridgway
College Hospital,
Summary: Teicoplanin was used to treat 94 hospital in-patients of confirmed or presumed Gram-positive infections over a period of 12 months. Eighty-five patients were subsequently found to be evaluable; 31 had soft tissue infections, 10 endocarditis, 8 urinary tract infections, 12 septicaemias, 2 chest infections, 7 osteomyelitis or septic arthritis, and 15 were immunosuppressed patients with infected Hickman line site infections. The cure rate of the 85 evaluable episodes was 90% (76 cured). Teicoplanin was well tolerated intravenously and intramuscularly. Adverse reactions occurred in five patients. One patient suffered high tone hearing loss, two patients suffered transient rash, one developed a drug fever and one patient who had concomitant gentamicin developed vestibular damage. It is concluded that teicoplanin is a relatively safe and effacacious treatment for Gram-positive infection. Introduction
Teicoplanin is a new glycopeptide antibiotic produced from the fermentation products of Actinoplanes teichomyceticus. It is a bactericidal antibiotic interfering with cell wall synthesis ‘in a manner similar to Unlike vancomycin, it has a long half-life of the order of vancomycin. 70-lOOh, can be given by fast iv injection or by im injection and is slightly more active than vancomycin in vitro. These properties make it an attractive alternative to vancomycin therapy. The aim of this study was to ascertain the safety and efficacy of teicoplanin in the treatment of Gram-positive infection. Methods
Over a period of 12 months 94 hospital in-patients with confirmed or presumed infections caused by Gram-positive organisms were treated. The drug was given, whenever practicable, as a loading dose of 400mg intravenously followed by daily im or iv doses of 200mg for periods ranging from 1 to 61 days. Of the 85 evaluable patients 31 had soft tissue infections, 10 endocarditis, 8 urinary tract infections; there were 12 septicaemias, 2 chest infections, 7 patients with osteomyelitis or septic arthritis and 15 immunosuppressed patients with infected Hickman line site infections. 01954701/86/07A101+03
0 1986 The Hospital
SO3 00/O
101
Infection
Society
A. H. Williams
et al.
Results
The clinical evaluation of the 85 evaluable patients is shown in Table I. Nine courses of treatment could not be evaluated because of protocol violation, adverse events or death from concurrent disease. The clinical cure rates among the 85 evaluable episodes were: 100% for soft tissue infections, urinary tract infections, chest infections, septicaemia and osteomyelitis, and 70% for endocarditis. The outcome was satisfactory in 61% of the evaluable Hickman line site infections. The overall success rate was 90% of the 85 evaluable treatments. Intramuscular injection was well tolerated. Adverse reactions were noted in five patients (5%) taking the form of transient rash in three patients, fever after the first injection in one patient [possibly related to a concurrent urinary tract infection (UTI)] and high tone (8 kHz) hearing loss in one patient. Table II shows the organisms isolated. Table Type
I. Clinical evaluation of 94 courses of treatment Evaluation
of infection
Soft tissue infections Endocarditis Urinary tract infection Septicaemia Chest infection Osteomyelitis Hickman line site infections
Cure Cure Cure Cure Cure Cure Line retained
No./total 31131 7110
818 12112
212 717 11/15
Overall 85 evaluable episodes treated with 76 cures (90% cures). Nine cases were not evaluable; two with chest infections because of intercurrent Gram-negative septicaemia in one patient and unrelated death after only two doses in the other; three with soft tissue infections and two cases of septicaemia because of protocol violations; one Hickman line site infection because of supervening fatal Gram-negative infection; and one Hickman line site infection due to death from graft versus host disease.
Discussion
Among the 51 patients with soft tissue infections, septicaemia, UTI, chest infections or osteomyelitis, no failures of treatment were seen. Ten patients were treated for endocarditis, five on prosthetic valves. Four of the five episodes of primary endocarditis and three of the five episodes of prosthetic valve endocarditis were cured (one was difficult to evaluate due to the withdrawal of treatment on day 17 due to a drug fever). Five patients were treated with teicoplanin alone (three cures) and in the others teicoplanin was combined with other antibiotics (two with gentamicin, one with flucloxacillin, one with gentamicin plus rifampicin and one with rifampicin), with three cures out of five.
Teicoplanin Table
II.
in Gram-positive
Organisms
Total
on evaluable
aureus
103
cases
Eradication and marked reduction
Organism Methicillin-sensitive Staphylococcus Methicillin-resistant Staph. aureus Streptococcus haemolyticus: group A group G group B Str. faecalis Str. milleri Clostridium perfringens Coagulase-negative staphylococci Str. mitior Str. sanguis Str. bovis Micrococcus
isolated
infections
13 12 9 3 2 9 1 1 15 1 1 1
Persistence 1
6
1 68
8
The difficulty of treating infections, whether endocarditis or Hickman line associated, in the presence of foreign bodies is well recognized. The treatment outcome in these patients seem remarkably good. One patient with a coagulase-negative staphylococcal infection of a ventriculo-atria1 shunt was also treated successfully. We are grateful to the Merrell Dow Research Institute for financial support and to Dr Peter Southgate for advice and encouragement. Our colleagues Dr Alison Webster and Dr Peter Wilson have given much help with this continuing study. We are grateful to many clinical colleagues for permission to treat and report on their patients.