Results from the Survey of Antibiotic Resistance (SOAR) 2015-17 in Pakistan: data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

Abstract

To determine antibiotic susceptibility of community-acquired respiratory tract infection (CA-RTI) isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2015-17 from Pakistan. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. A total of 94 S. pneumoniae and 122 H. influenzae isolates were collected. Susceptibility to penicillin was noted in 23.4% of the S. pneumoniae isolates by CLSI oral/EUCAST low-dose IV breakpoints, although by CLSI IV and EUCAST high-dose breakpoints all isolates were characterized as susceptible. Susceptibility to trimethoprim/sulfamethoxazole (10.6%), macrolides (33%) and cefaclor (28.7%) was low but higher susceptibility was observed to ceftriaxone (100%), amoxicillin and amoxicillin/clavulanic acid (98.9%), cefuroxime (oral, 97.9%), cefpodoxime (96.8%), fluoroquinolones (93.6%-96.8%) and cefdinir (76.6%) by CLSI breakpoints. However, using EUCAST breakpoints, susceptibility to cefpodoxime (70.2%) and cefuroxime (oral, 61.7%) was reduced. H. influenzae isolates were almost all β-lactamase negative (96.7%). Using CLSI breakpoints, ≥93.4% of isolates were susceptible to all antibiotics tested except fluoroquinolones (75.4%-77.1%) and trimethoprim/sulfamethoxazole (41%). The proportion of isolates susceptible using EUCAST breakpoints was similar or identical for penicillins, trimethoprim/sulfamethoxazole and the cephalosporins that have EUCAST breakpoints; the proportion of isolates susceptible using EUCAST breakpoints was similar or identical to that using CSLI breakpoints except for cefuroxime (oral), where only 1.6% of isolates were considered susceptible. Susceptibility of H. influenzae to fluoroquinolones was also lower by EUCAST breakpoints (33.6%-34.4%). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. Antibiotic susceptibility in these important respiratory tract pathogens varied in Pakistan based on different breakpoints. These data are important for empirical therapy choices in the treatment of CA-RTIs.