Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries

BACKGROUND: Improving the quality of hospital antibiotic use is a major goal of WHO's global action plan to combat antimicrobial resistance. The WHO Essential Medicines List Access, Watch, and Reserve (AWaRe) classification could facilitate simple stewardship interventions that are widely applicable globally. We aimed to present data on patterns of paediatric AWaRe antibiotic use that could be used for local and national stewardship interventions. METHODS: 1-day point prevalence survey antibiotic prescription data were combined from two independent global networks: the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children and the Global Point Prevalence Survey on Antimicrobial Consumption and Resistance networks. We included hospital inpatients aged younger than 19 years receiving at least one antibiotic on the day of the survey. The WHO AWaRe classification was used to describe overall antibiotic use as assessed by the variation between use of Access, Watch, and Reserve antibiotics, for neonates and children and for the commonest clinical indications. FINDINGS: Of the 23 572 patients included from 56 countries, 18 305 were children (77·7%) and 5267 were neonates (22·3%). Access antibiotic use in children ranged from 7·8% (China) to 61·2% (Slovenia) of all antibiotic prescriptions. The use of Watch antibiotics in children was highest in Iran (77·3%) and lowest in Finland (23·0%). In neonates, Access antibiotic use was highest in Singapore (100·0%) and lowest in China (24·2%). Reserve antibiotic use was low in all countries. Major differences in clinical syndrome-specific patterns of AWaRe antibiotic use in lower respiratory tract infection and neonatal sepsis were observed between WHO regions and countries. INTERPRETATION: There is substantial global variation in the proportion of AWaRe antibiotics used in hospitalised neonates and children. The AWaRe classification could potentially be used as a simple traffic light metric of appropriate antibiotic use. Future efforts should focus on developing and evaluating paediatric antibiotic stewardship programmes on the basis of the AWaRe index. FUNDING: GARPEC was funded by the PENTA Foundation. GARPEC-China data collection was funded by the Sanming Project of Medicine in Shenzhen (SZSM2015120330). bioMérieux provided unrestricted funding support for the Global-PPS

Emergence of CTX-M-15 extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates in Bosnia and Herzegovina

Fifty-seven nosocomial Klebsiella pneumoniae isolates producing extended-spectrum β-lactamases (ESBLs) were collected between February 2007 and November 2007 in different wards of the Sarajevo (Bosnia-Herzegovina) reference hospital. These isolates comprise two major epidemic pulsed-field electrophoresis-defined clones plus two minor clones. In addition to the ESBL-mediated resistance, all strains uniformly showed resistance to ciprofloxacin, gentamicin and tobramycin. The β-lactamases involved in this resistance phenotype were TEM-1, SHV-1, and CTX-M-15, as demonstrated by isoelectric focusing, PCR amplification, and sequencing. TEM-1 and CTX-M-15 β-lactamases, as well as the aminoglycoside resistance determinants, were encoded in plasmids that could be transferred to Escherichia coli by conjugation. In three of the infected patients with the predominant clone, cefoxitin resistance development (MICs >128 mg/L) was documented. The analysis of the outer membrane proteins of the cefoxitin-susceptible and cefoxitin-resistant isolates revealed that the former expressed only one of the two major porins, OmpK36, whereas in the latter, the expression of Ompk36 was altered or abolished. This is the first report of CTX-M-15-producing K. pneumoniae in Bosnia-Herzegovina. Furthermore, we document and characterize for the first time cefoxitin resistance development in CTX-M-15-producing K. pneumoniae