Defining the Aetiology and Antimicrobial Susceptibility Patterns of the Predominant Bacteria Associated with Bloodstream Infections at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam

Bloodstream infections (BSI) are among the most common critical diseases that require intensive care and continuous surveillance. According to many multinational antimicrobial resistance surveillance schemes, Asia represents a substantial reservoir of clinically relevant antimicrobial resistant genes. These genes include extended spectrum Beta lactamases (ESBLs) and AmpC lactamases in the Enterobacteriaceae, methicillin-resistance genes in Staphylococcus aureus, carbapenemase-resistance genes in Gram-negative bacilli and vancomycin-resistance genes in enterococcus. Asian countries are also burdened with high prevalence of HIV, in which BSI can be a major health problem in these immunocompromised people. Currently, there are no national data regarding the pathogens associated with BSI in Vietnam. Additionally, there are limited BSI data in specific populations, such as those infected with HIV, and there is limited information regarding the distribution and epidemiology of hospital-acquired and community-acquired infections. Data contributing to our understanding of common antimicrobial resistance mechanisms or profiles, including ESBLs, AmpC, KPC, and MRSA in BSI pathogens in Vietnam are also scarce. The aims of this study were to describe the characteristics of BSI in the Hospital for Tropical Diseases (HTD), a tertiary healthcare facility for infectious diseases in the south of Vietnam. I aimed to identify the most common BSI pathogens and their antimicrobial resistance profile in the context of the aetiological agent and disease outcome. Further, I aimed to define the specific types of ESBLs and AmpC genes circulating in Gram-negative bacilli isolated from BSI patients. I further describe the clinical and laboratory characteristics of BSI infections caused by the non-typhoidal Salmonella (iNTS) a particular group of BSI pathogens that are prevalent in immunocompromised patients. Lastly, I aimed to validate an automatic antimicrobial susceptibility testing system for Salmonella isolates in comparison to manual testing methods. I found that BSI in HTD was characterised by a low annual blood culture positivity rate (7%) and a declining annual trend of mortality. A high proportion of BSI was from patients in the intensive care unit (33%) and the HIV ward (22%). I report an increased trend of multidrug-resistant Gram-negative and Gram-positive pathogens in both hospital-acquired and community-acquired BSI infections. I additionally report a case study for BSI due to Vibrio cholerae non-O1, non-O139 and the first-ever outbreak report of Brucella melitensis in Vietnam. I performed molecular characterisation for all Gram-negative organisms isolated over a four-year period that exhibited reduced susceptibility against 3rd cephalosporin. Phenotypic screening found 304/1,017 (30%) organisms that were resistance to third generation cephalosporins; 172/1017 (16.9%) of isolates exhibited ESBL activity, 6.2% (63/1017) had AmpC activity, and 0.5% (5/1017) had both ESBL and AmpC activity. E. coli and Aeromonas spp. were the most common organisms associated with ESBL and AmpC phenotypes, respectively. There was no significant difference (p>0.05) between antimicrobial resistance phenotypes of organisms associated with community and hospital-acquired infections. I retrospectively identified 102 cases of iNTS infections in HTD between 2008 and 2013. Of 102 iNTS patients, 71% were HIV-infected, >90% were adults, 71% were male, and 33% reported intravenous drug use. Twenty-six/92 (28%) patients with a known outcome died; HIV infection was significantly associated with death (p=0.039). S. Enteritidis (Sequence Type (ST)11) (48%, 43/89) and S. Typhimurium (ST19, 34 and 1544) (26%, 23/89) were the most commonly identified serovars; S. Typhimurium was significantly more common in HIV-infected individuals (p=0.003). Through comparison of different antimicrobial testing methods for Salmonella, I identified a problematic agreement or errors were with quinolone antimicrobials. I found that the VITEK automatic antimicrobial susceptibility testing system did not produce satisfactory results for the Salmonella. However, the disk-diffusion method was a more reliable method for testing beta-lactams, azithromycin, and trimethoprim-sulfamethoxazole. In conclusion, BSI in HTD are characterised with an increasing trend of multi-drug resistant organisms that will challenge clinical and laboratory diagnostic as and future treatment options