A Randomized Double Blinded Comparison of Ceftazidime and Meropenem in Severe Melioidosis

• Status: Unknown status
• Trial end date: 2010-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Melioidosis, an infection caused by the bacterium Burkholderia pseudomallei, is a major cause of community-acquired septicaemia in northeast Thailand. Common manifestations include cavitating pneumonia, hepatic and splenic abscesses, and soft tissue and joint infections. Despite improvements in diagnostic procedures and treatment, the mortality of severe melioidosis remains unacceptably high - approximately 35% with currently used antibiotics (ceftazidime or co-amoxiclav). There is clear evidence that antibiotics can affect mortality; the use of ceftazidime rather than previous regimens (doxycycline + chloramphenicol + co-trimoxazole) led to a 50% reduction in mortality from 80% to 35%. However, the mortality in the first 48 hours has not been altered by any treatment regimen. A key question is whether alternative antibiotics could improve early outcome. The hypothesis tested is that meropenem is superior to ceftazidime in terms of mortality for the treatment of melioidosis.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Oxford
• Collaborators: Mahidol University; Wellcome Trust
• Treatments: Ceftazidime; Meropenem; Thienamycins

Criteria

Inclusion criteria (all criteria must be satisfied)

A. Community acquired sepsis, and melioidosis is suspected:

Suspected melioidosis (12): all of the following are defined as 'clinically probable' melioidosis

• A history of frequent contact with soil or surface water in the endemic area

• At least one of the following risk factors: diabetes mellitus, chronic renal failure or renal calculi, thalassaemia, aplastic anaemia or steroid abuse

• An illness compatible with melioidosis, including the presence of sepsis, acute pneumonia, acute pyelonephritis, septic arthritis, parotid disease or skin or soft tissue infection, or

• An evidence of intra-abdominal suppuration (hepatic or splenic abscesses) regardless of risk factors or exposure history

Sepsis: defined as patients who have Systemic Inflammatory Response Syndrome (SIRS) - two or more of the following, clinically ascribed to infection:

• Fever: temperature >38°C or <36°C

• Tachycardia: heart rate >90 beats/min

• Tachypnoea:

1. Respiratory rate >20 breaths/minute; or

2. PaCO2 <32 mmHg; or

3. Mechanical ventilation

• White cell count >12,000 cells/mL or <4,000 cells/mL or >10% band forms B. Age > 14 years. C. Need hospitalisation and intravenous antibiotic administration. D. Willingness to participate in the study and written, informed consent obtained from the patient.

Exclusion Criteria (any one of the following):

A. Pregnant or lactating women. B. Known hypersensitivity to meropenem or ceftazidime. C. Previous isolate with known resistance to ceftazidime or meropenem. D. Patients not expected to remain in hospital for treatment. E. Patients with community-acquired sepsis with cultures positive for other organisms.

F. Patients treated with antibiotics active against B. pseudomallei (including ceftazidime, amoxicillin-clavulanate, meropenem) for this episode for greater than 24 hours.