Extensively Drug-Resistant Typhoid

Symptoms of typhoid fever often include high fever, weakness, stomach pain, headache, cough, and loss of appetite. Some people have diarrhea or constipation. In rare cases, typhoid fever can be fatal. Treatment with antibiotics is essential.

EXTENSIVELY DRUG RESISTANCE TYPOID

AN EMERGIGING CHALLENGE 

 Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S. Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third generation cephalosporin’s in Sindh, Pakistan, which we classify as extensively drug resistant (XDR).

5648 culture confirmed XDR typhoid cases have emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of travel-associated XDR typhoid has recently been identified in the United Kingdom.

https://doi.org/10.1128/mBIO .00105_18

CASE DEFINATION OF XDR

Any person with major sign/symptoms including fever greater then 100F for more then 3 out of 7 consecutive days without any obvious cause of infection, with anyone of the gastrointestinal symptoms (abdominal pain, anorexia, vomiting, diarrhea or constipation) or minor symptoms such as rose spots , bradycardia, lethargy and coated tongue  along with the laboratory confirmed S.TYPHI isolation from blood , bone marrow, body fluids/stool or a clinically compatible case that is laboratory confirmed  which is resistant to ampicillin, chloramphenicol, co trimoxixole , ciprofloxacin  and ceftriaxone .

ALERT: three suspected cases in a defined geographical area within two incubation periods

OUT BREAK THRESHOLD: two laboratory confirmed cases in a defined geographical area within two incubation period 

MANAGEMENT GUIDELINES

  • Blood cultures is the gold standard for the diagnosis and should always be sent
  • Serological tests for typhoid should not be ordered and relied upon
  • Evaluate for other causes of fever malaria dengue etc.
  1. Commence treatment for suspected typhoid with either ceftriaxone 50-75 mg / kg in one to two divided doses or ceftriaxone 50-75 mg/kg in one to two divided doses.
  2. If by day 5 of antibiotics, patient not improving and blood culture negative refer to a secondary or tertiary care Centre
  3. If the blood cultures show that the organism is sensitive to any 1st line drugs switch to 1st line  drug to complete a total of 14 days’ therapy
  4. If the blood cultures grow a Multi Drug Resistant (MDR) Typhoid continue the same treatment as started empirically to complete a total of 14 days
  5. If the blood cultures show that the isolate is Extensive Drug Resistant Typhoid (XDR). Following regimen may be considered;
  1. If the patient is able to tolerate orally and no complications commence Azithromycin (Patient weigh < 60 kg- use 1 gm loading dose of Azithromycin followed 24 hrs. later by Azithromycin 500 mg po orally for 7-10 days) Pediatric dose of Azithromycin 20 mg/ kg once a day for 7-10 days.
  2. If the patient requires in patient management or complicated typhoid, then refer to tertiary care center. Start carbapenem (Imipenem: 500 mg q6h for days or deescalate to oral Azithromycin (not more than 10 days) once tolerating oral to complete 14 days) or (Meropenem: 60 mg/ kg/ day in three divided doses. If meningitis 120 mg/ kg/day in 3 divided doses (all should be given in extended infusion over 2-4 hrs.) or De-escalate to oral Azithromycin (not more than 10 days)

COMPLICATED TYPHIOD:

Steroids (dexamethasone 3 mg/ kg loading and then 1 mg / kg q6h for 48 hrs.) are indicated in patients with suspected or culture proven typhoid patients with obstruction, shock, Jaundice, drowsiness, severe abdominal pain and intestinal hemorrhage, features of septicemia.

Vaccination: 2 types of vaccines targeting Salmonella entrica serovar Typhi are available in the country: vaccination is recommended for all health care workers and subject to availability should be offered to all households of the patient on recovery as a short term measure to reduce the burden of the disease. 

PREVENTION

PRACTICE SAFE EATING AND DRINKING HABITS

Because the bacteria that cause typhoid fever are spread through contaminated food and water, you can reduce your risk of infection in several ways:

  • Follow safe food and water guidelines.
  • Wash your hands often, especially before eating.
  • Avoid eating food prepared by anyone who is sick or has recently been sick.

VACCINE / ROLE OF IMMUNIZATION

Typhoid vaccines protects 50 to 80 percent of recipients and should be offered to patients with increased risk of exposure

2 types of vaccination targeting SALMONELLA ENTERICA SEROVAR Typhi are available in the country. vaccination is recommended for 

  • All health care workers.
  • All household of the patients subject to availability ‘.
  • The patients on recovery.  

 

Reference

https;//doi.org/10.1128/mbio.00105-18

http://mbio.asm.org/

http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2672.1999.00514.x/pdf

http://apps.who.int/medicinedocs/documents/s16330e/s16330e.pdf

http://www.who.int/medical_devices/publications/basic_lab_procedures_clinical_bact/en/