The Burden of Penicillin and other Antibiotic Allergy Labels and Antimicrobial Resistance in Low and Middle-Income Countries (PALAR study)

Background**:**

Antimicrobial resistance (AMR) is a major global public health problem claiming an estimated 700,000 lives/year. Multiple factors contribute to AMR and research in High Income Countries (HICs) has shown that antibiotic allergy labels (AALs), specifically penicillin allergy labels (PALs) significantly enhance the risk of AMR. Such information is not available for low-middle income countries(LMIC).

Methods:

This is an Observational study done in 4 Low to middle income countries, India, Sri Lanka, Indonesia and Egypt. A target area will be identified for the AMR arm and the AAL arm of the study at each institution.

The following drug-bug combinations from the WHO Global AMR Surveillance System (GLASS) manual will be followed for AMR surveillance:

•          Escherichia coli vs.  3rd generation cephalosporins and fluoroquinolones

•          Klebsiella pneumoniae vs. 3rd generation cephalosporins and carbapenems

•          Staphylococcus aureus vs. oxacillin or cefoxitin

•          Streptococcus pneumoniae vs. penicillin or oxacillin

•          Salmonella species vs. fluoroquinolones

•          Shigella species vs. fluoroquinolones

•          Neisseria gonorrhoeae vs. 3rd generation cephalosporins

 Antimicrobial susceptibility testing for priority pathogens will be carried out in line with international standards. The status of the isolates with regard to whether isolates are susceptible, intermediate or resistant (S/I/R) according to clinical breakpoints defined by EUCAST or CLSI. Zone sizes (mm) will also be measured and recorded. At the extended and advanced levels, minimum inhibitory concentrations (MICs) will be determined, e.g., by micro broth dilution (manual or automated) or gradient diffusion tests such as E-Tests. MIC values will be recorded (in case breakpoints change in the future).

 In order to assess the impact of AALs on the development of AMR, we will analyze patients presenting with both invasive and non-invasive infections with Staphylococcus aureus, enterococcal species, extended-spectrum beta-lactamase (ESBL) producing Enterobacterales and carbapenem-resistant organisms. Data will be collected in bacterial sets, using age and sex-matched controls both for invasive and non-invasive infection based upon the following combinations:

 â€¢          Staphylococcus aureus vs methicillin-resistant Staphylococcus aureus

•          vancomycin-sensitive enterococci vs vancomycin-resistant enterococci

•          ESBL-nonproducing vs ESBL producing Enterobacterales

•          Carbapenem-sensitive vs Carbapenem-resistant organisms (genus and species of the organism to be matched).

Informed consent would be obtained and the data will be captured on a standard study.

Results:

Prevalence of AALs will be calculated at each site and across all sites. Descriptive statistics will be generated as per study aims and objectives. A descriptive analysis will be carried out to report frequency distribution as per WHO AWaRe classification.  Incidence rates of AMR will be reported (overall and for individual bacteria as stated above) for invasive and non-invasive infections.