Comparison of Two Drugs Regimen in Treatment of Complicated Typhoid Fever in Children

Treatment of 21st Century Typhoid Fever in Children;Open Label Mono vs Combination Drug Therapy

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

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.

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