Comparison of Two Drugs Regimen in Treatment of Complicated Typhoid Fever in Children ([XDRTYPHOID])

Ziauddin University

Status and phase: Completed; Phase 4

Conditions: Typhoid Fever

Treatments: Drug: Azithromycin Powder; Drug: Meropenem Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT04154722

0980419HRPED

Details and patient eligibility

About

This study evaluates whether XDR Typhoid fever in children can be effectively treated with monotherapy (meropenum alone), or a combination (meropenum and azithromycin).

Full description

Complicated XDR Enteric fever is a very serious systemic disease, caused by an extremely resistant mutant strain of Salmonella Typhi ( the H58 S. Typhi superbug,) that as the name suggests is resistant to not only the first but also the second tier drugs conventionally used for treatment of the same. And as such, warrants immediate antibiotic therapy, but in view of the extended antimicrobial resistance the treatment options are limited to only two effective drugs viz Carbepenem and Azithromycin, as per culture sensitivity.

So far, in the absence of universal standardized treatment protocols for XDR complicated typhoid fever in children, random use of either one or both in combination is the current practice.

However, keeping antibiotic stewardship in mind, it is imperative to ascertain whether meropenum alone is effective or should be combined with azithromycin in the treatment of this serious disease.

Our study therefore compares the efficacy of monotherapy with meropenum or combination with azithromycin based on clinical and microbiologic remission, shortened hospital stay and less chances of relapse in order to then formulate a standardized protocol to treat complicated XDR typhoid in children thus preventing yet further antimicrobial resistance.

Enrollment: 126 patients

Sex: All

Ages: 6 months to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patients with extended drug resistant typhoid fever defined as culture proven typhoid fever caused by Salmonella Typhi or Para typhi resistant to Ampicillin, Chloramphenicol,Co trimoxazole,Quinolones and Ceftriaxone along with two or more of the following condition

• High grade fever spikes for more than three days
• Refusal to eat or drink
• Drowsy or Unconscious
• Convulsions
• Dehydration due to diarrhea or vomiting
• Abdominal distension with or without tenderness
• Bleeding diathesis like petechial rash, gum bleed, melena
• Jaundice or alanine transaminase more than twice of the normal range
• Thrombocytopenia less than fifty thousand
• Increase Prothrombin time and activated partial thromboplastin time
• Electrolyte imbalance like hyponatremia, hypernatremia, hypokalemia, hyperkalemia, metabolic acidosis
• Hypoglycemia
• Signs of shock like cold and mottled skin, feeble pulses, tachycardia, decreased blood pressure

Exclusion criteria

• Not given informed consent
• Children who need ventilator or two inotrope support
• Severe malnutrition/immunocompromised patient

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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126 participants in 2 patient groups

meropenum and azithromycin group

Experimental group

Description:

inj meropenum 20mg/kg/dose I/v in 3 divided doses and syp azithromycin 20mg/kg/day in 2 divided doses.

Treatment:

Drug: Meropenem Injection

Drug: Azithromycin Powder

meropenum group

Active Comparator group

Description:

inj meropenum 20mg/kg/dose I/v in 3 divided doses

Treatment:

Drug: Meropenem Injection