Choice of Antibiotics For the Treatment of Sepsis (Infection) in Newborn Babies

Completed

Conditions: Bacterial sepsis of newborn, unspecified,

Registration Number: CTRI/2019/03/017960

Lead Sponsor: Banaras Hindu University

Brief Summary: Antibiotics are empirically used for the treatment of neonatal sepsis. Ampicillin and gentamicin regimen is generally the first choice. In view of rising antibiotic resistance and occurrence of Staphylococcus aureaus as a common pathogen in India in both early- and late-onset sepsis, co-amoxyclav and amikacin may be a better choice. In this study we will compare the efficacy and safety of ampicillin and gentamicin versus co-amoxyclav and amikacin as an initial empirical therapy in the treatment of neonatal sepsis. Neonatal sepsis will be suspected on the basis of modified criteria given by European Medicines Agency, 2010. Sepsis work-up will consist of total WBC count, absolute neutrophil count, I/T ratio, platelet count, CRP, Procalcitonin and blood culture. CRP will be repeated 12-24 hours later in an unwell baby if initial result is less than 10 mg/dl. Lumbar puncture will be done in all cases of suspected sepsis. In critically sick newborns lumbar puncture will be delayed by 24-48 hours.Other relevant investigations such as chest xray, arterial blood gases, renal and liver profile, cranial sonography and echocardiography will be done as per need.

Primary outcome variable is treatment failure which is defined as need to change initial antibiotic regimen within 72 hours of enrollment or earlier if clinician considers it necessary in view of deteriorating clinical condition of the baby, or not cured by 7 days after enrollment. Antibiotics will be changed under the following circumstances (one or more): 1. failure to improve or worsening clinical status, 2. new or worsening infiltrates on chest xray, 3. CRP increases by more than 10 mg/dl in an unwell newborn, 4. isolation of bacteria resistant to initial antibiotic regimen in an unwell newborn.

In the event of treatment failure as defined above, antibiotics will be changed as per blood/cerebrospinal fluid culture culture report, or empirically keeping in mind the sensitivity pattern of prevalent organisms in the unit. Ampicillin and gentamicin will be replaced empirically with piperacillin-tazobactam and amikacin. Likewise, co-amoxyclav will be replaced empirically with piperacillin-tazobactam while amikacin will be continued as such, or modified as per culture report. In case of meningitis cefotaxime will be added empirically to the existing regimen. Sepsis screen and blood culture will be repeated in the event of treatment failure and before change of antibiotics. Duration of antibiotics will be 7 days in culture-negative sepsis, 10 days in culture-positive sepsis and pneumonia and 21 days in meningitis. Antibiotics will be administered intravenously.

Newborns will be closely monitored for clinical improvement/deterioration, adverse effects of therapy and daily progress using a predesigned proforma. Newborns will be followed up at one week and one month of age for general well being and any other problem.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 312

Inclusion Criteria

Clinical Symptoms (2 or more) 1 If core body temperature more than 38.5Â°C or less than 36Â°C or temperature instability.
2 Cardiovascular instability: bradycardia(heart rate below 80/minute) or tachycardia(heart rate above 180/minute) or reduced urinary output (less than 1 ml/kg/hour)or hypotension requiring volume or inotropic support, or mottled skin or capillary refilling time more than 3 seconds 3 Respiratory instability: apnea(cessation of breathing for more than 20 seconds) or tachypnea(respiratory rate more than 60/minute)or episodes or increased oxygen requirement by more than 10% or requirement of ventilatory support 4 Petechial rash or sclerema 5 Feeding intolerance or poor sucking or abdominal distension 6 Central nervous system: irritability or lethargy or hypotonia or seizures 7 Cellulitis or skin ulceration Laboratory signs (2 or more) 1 White blood cells (WBC) count: below 4,000/cubic mm or above 20,000 cubic mm 2 Platelet count below 100,000 cubic mm 3 Immature to total neutrophil ratio above 0.2 4 C reactive protein above 10 mg/L or Procalcitonin levels above hourly reference values after birth 5 Glucose intolerance: hyperglycemia (blood glucose above 180 mg/dL) or hypoglycemia (blood glucose below 45mg/dL) 6 Metabolic acidosis: Base excess (BE) below -10 mEq/L or Serum lactate above 2 mMol/L 7 Chest xray suggestive of bronchopneumonia 8 Cerebrospinal fluid changes suggestive of septic meningitis.

Exclusion Criteria

1 Newborns receiving antibiotics for 3 days or less for rule out sepsis 2 Surgical conditions and major congenital anomalies 3 Failure to obtain consent 4 Receipt of antibiotics prior to randomization.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Treatment failure will be defined as a need for change of initial antibiotic regimen within 72 hours of enrollment, or earlier if treating physician considers it necessary, or not cured by day 7 after enrollment.	7 days

Secondary Outcome Measures

Name	Time	Method
1. Death at 3 days of age	2.Death at one week of age

Trial Locations

Locations (1): SS Hospital
🇮🇳
Varanasi, UTTAR PRADESH, India
SS Hospital
🇮🇳Varanasi, UTTAR PRADESH, India
Prof Ashok Kumar
Principal investigator
9415300370
ashokkumar_bhu@hotmail.com