Background: Healthcare associated infections (HCAI) and antimicrobial resistance are principal threats to the patients of intensive care units and are the major determining factors for patient outcome. They are associated with increased morbidity, mortality, excess hospitalization and financial costs. The present study is an attempt to investigate the spectrum and antimicrobial resistance of bacterial isolates involved in healthcare associated infections (HCAI) in the patients of a critical care unit at a tertiary care university hospital in Kathmandu, Nepal.

Pseudomonas aeruginosa (P. aeruginosa) is one of the most common nosocomial pathogens worldwide. Although the emergence of multidrug-resistant (MDR) P. aeruginosa is a critical problem in medical practice, the key features involved in the emergence and spread of MDR P. aeruginosa remain unknown. This study utilized whole genome sequence (WGS) analyses to define the population structure of 185 P. aeruginosa clinical isolates from several countries. Of these 185 isolates, 136 were categorized into sequence type (ST) 235, one of the most common types worldwide. Phylogenetic analysis showed that these isolates fell within seven subclades. Each subclade harbors characteristic drug resistance genes and a characteristic genetic background confined to a geographic location, suggesting that clonal expansion following antibiotic exposure is the driving force in generating the population structure of MDR P. aeruginosa. WGS analyses also showed that the substitution rate was markedly higher in ST235 MDR P. aeruginosa than in other strains. Notably, almost all ST235 isolates harbor the specific type IV secretion system and very few or none harbor the CRISPR/CAS system. These findings may help explain the mechanism underlying the emergence and spread of ST235 P. aeruginosa as the predominant MDR lineage.

The widespread use of tracheal intubation and mechanical ventilation to support the critically ill patients increases the risk of development of tracheobronchitis and bronchopneumonia. This cross-sectional study was conducted with an aim to isolate and identify bacterial pathogens from tracheal aspirates producing extended-spectrum β-lactamase (ESBL), AmpC β-lactamase, and metallo-β-lactamase (MBL) from August 2011 to April 2012 at National Institute of Neurological and Allied Sciences (NINAS), Kathmandu, Nepal. ESBL was detected by combined disk assay using cefotaxime and cefotaxime with clavulanate, AmpC β-lactamase by inhibitor-based method using cefoxitin and phenylboronic acid, and MBL by Imipenem-EDTA combined disk method. 167 bacterial strains were isolated from 187 samples and majority of them were Acinetobacter spp. followed by Klebsiella pneumoniae with 32.9% and 25.1%, respectively. 68.8% of isolates were multidrug resistant (MDR) and Acinetobacter spp. constituted 85.4%. ESBL, AmpC β-lactamase, and MBL were detected in 35 (25%), 51 (37.2%), and 11 (36.7%) isolates, respectively. Pseudomonas spp. (42.8%) were the predominant ESBL producer while Acinetobacter spp. were the major AmpC β-lactamase producer (43.1%) and MBL producer (54.5%).

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Within Nepal, geographic, social, and economic barriers greatly limit access to allopathic health care. The country therefore offered the opportunity to evaluate the effect of antibiotic accessibility (as measured by allopathic medicine consumption) on antibiotic resistance in the normal intestinal flora. The aerobic gram-negative fecal flora of 33-34 healthy adults from each of 3 villages with different access to health care facilities in Kathmandu were examined for antibiotic susceptibility. The frequency of antibiotic resistance decreased significantly with increasing distance from Kathmandu and decreasing population density but did not reflect contact with health care providers or individual medicine consumption. The findings suggest that an individual's overall exposure to antibiotics and antibiotic-resistant bacteria (resulting from close proximity to other community members and to sources of accessible allopathic health care, such as in the vicinity of Kathmandu), has an equal or greater impact on an individual's carriage of antibiotic-resistant bacteria than does direct consumption of antibiotics.