Journal of Chemotherapy

ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20

Aztreonam plus Vancomycin versus Gentamicin plus Piperacillin as Empirical Therapy for the Treatment of Fever in Neutropenic Patients: a Randomised Controlled Study S.M. Kelsey, E. Shaw & A.C. Newland To cite this article: S.M. Kelsey, E. Shaw & A.C. Newland (1992) Aztreonam plus Vancomycin versus Gentamicin plus Piperacillin as Empirical Therapy for the Treatment of Fever in Neutropenic Patients: a Randomised Controlled Study, Journal of Chemotherapy, 4:2, 107-113, DOI: 10.1080/1120009X.1992.11739149 To link to this article: http://dx.doi.org/10.1080/1120009X.1992.11739149

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Journal of Chemotherapy

Aztreonam plus Vancomycin versus Gentamicin plus Piperacillin as Empirical Therapy for the Treatment of Fever in Neutro penic Patients: a Randomised Controlled Study S.M. KELSEY* - E. SHAW** A.C. NEWLAND*

Summary - - - - - - - - - - - - - - - -

The efficacy of aztreonam in combination with vancomycin was compared with that of gentamicin plus piperacillin as empirical antibiotic treatment for fever in 61 neutropenic patients. Aztreonam plus vancomycin was as effective, but no more effective, than gentamicin plus piperacillin. Aztreonam showed excellent clinical and in vitro efficacy against Gramnegative pathogens. Failure to respond to aztreonam plus vancomycin was, in most cases, due to presumed or documented fungal infection; by contrast, failure to respond to gentamicin plus piperacillin was frequently to be due to resistant or superadded infection with Gram-positive bacteria. Key words: Neutropenia, fever, vancomycin, aztreonam.

Departments of *Haematology and **Microbiology, the Royal London Hospital, London El lBB, United Kingdom. Correspondance to: Dr. SM Kelsey, Department of Haematology, The Royal London Hospital, London El1BB, UK. © Edizioni Riviste Scientifiche - Firenze

Vol. 4 - n. 2 (107 -113) - 1992

INTRODUCT ION

A combination of a ureidopenicillin and an aminoglycoside has long been regarded as the mainstay of empirical antibiotic therapy in febrile patients rendered neutropenic following chemotherapy for haematological malignancy!. Newer antibiotics with broad spectrum activity against Gram-negative organisms, such as ciprofloxacin and ceftazidime, have been successfully used as single agents to empirically treat fever in neutropenic patients 2 ' 3 • However, treatment failures due to Gram-positive bacterial infection are common 4 • 5 and in many cases the addition of a specific anti-Gram-positive agent to the regimen, such as benzylpenicillin 6 , teicoplanin 7 or vancomycin 8 has been thought to be justified. Aztreonam is a monobactam antibiotic with wide ranging in-vivo an in-vitro activity against aerobic Gram-negative organisms commonly en9 10 countered in nosocomial infections • • It is highly resistant to beta lactamase-mediated hydrolysis. Aztreonam has no activity against Gram-positive organisms. We therefore conducted a randomised study of the efficacy of aztreonam plus vancomycin for empirical treatment of febrile neutropenic patients compared with our standard regimen of gentamicin plus piperacillin. Vancomycin was added for its specific anti-Gram-positive cover. The efficacy of aztreonam as a single agent for empirically treating Gram-negative bacteraemia in these patients was assessed. In addition, we report our experience using vancomycin as a first line antibiotic in these circumstances. ISSN 1120-009X

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S.M. KELSEY • E . SHAW • A.C. NEWLAND

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PATIENTS AND METHODS

Sixty-one neutropenic patients rece1vmg chemotherapy or bone marrow transplant for haematological malignancy were entered into the study between January and December 1989. All patients were febrile as defined by a single temperature of 38.5°C or two consecutive readings of 38.0°C two hours apart not associated with administration of blood products. Neutropenia was defined as a total neutrophil count of less than 1.0 X 10 9 per litre. All patients were aged greater than 18 years and gave informed consent. Pregnant or nursing women, patients with a history of allergy to study antibiotics, and patients who had received antibiotics within the preceding five days other than gut decontamination, were excluded from the study. The study protocol was approved by the local Ethics Committee. Eligible patients were randomised to receive either vancomycin (Eli Lilly) plus aztreonam (Bristol Myers-Squibb) or gentamicin (Roussel) plus piperacillin (Lederle). Vancomycin was given as an intravenous infusion over one hour at a dose of 1g 12 hourly. Serum levels were monitored to keep peak levels between 25-35mg/ml and trough levels of less than 10mg/ml. Aztreonam was given as 2g 8 hourly as an IV bolus. A 120mg loading dose of gentamicin was followed by 80mg 8 hourly to achieve pre-dose troughs of

Aztreonam plus vancomycin versus gentamicin plus piperacillin as empirical therapy for the treatment of fever in neutropenic patients: a randomised controlled study.

The efficacy of aztreonam in combination with vancomycin was compared with that of gentamicin plus piperacillin as empirical antibiotic treatment for ...
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