Ten-year narrative review on antimicrobial resistance in Singapore

Antimicrobial resistance (AMR) results in drug-resistant infections that are harder to treat, subsequently leading to increased morbidity and mortality. In 2008, we reviewed the problem of AMR in Singapore, limiting our discussion to the human healthcare sector. Ten years later, we revisit this issue again, reviewing current efforts to contain it in order to understand the progress made as well as current and emerging challenges. Although a significant amount of work has been done to control AMR and improve antibiotic prescribing in Singapore, most of it has focused on the hospital setting, with mixed impact. The role of antibiotic use and AMR in food animals and the environment - and the link to human health - is better understood today. This issue of AMR encompasses both human health as well as animal/food safety, and efforts to control it will need to continually evolve to maintain or improve on current gains.

In Vitro Efficacy of Six Alternative Antibiotics against Multidrug Resistant Escherichia Coli and Klebsiella Pneumoniae from Urinary Tract Infections

<p><b>INTRODUCTION</b>Increasing resistance in Escherichia coli and Klebsiella pneumoniae to firstline antibiotics makes therapeutic options for urinary tract infections (UTIs) challenging. This study investigated the in vitro efficacies of 6 antibiotics against multidrug resistant (MDR) uropathogens.</p><p><b>MATERIALS AND METHODS</b>Minimum inhibitory concentrations to ceftibuten, cefpodoxime, fosfomycin, mecillinam, temocillin, and trimethoprim were determined against 155 MDR-isolates of E. coli and K. pneumoniae. The presence of extended-spectrum beta-lactamases (ESBL) and plasmid-borne AmpC enzymes was determined by phenotypic testing with genotyping performed by multiplex polymerase chain reaction.</p><p><b>RESULTS</b>Temocillin demonstrated highest susceptibility rates for both E. coli (95%) and K. pneumoniae (95%) when breakpoints for uncomplicated UTIs were applied; however, temocillin susceptibility was substantially lower when "systemic infection" breakpoints were used. Fosfomycin demonstrated the best in vitro efficacy of the orally available agents, with 78% and 69% of E. coli and K. pneumoniae isolates susceptible, respectively. The next most effective antibiotics were ceftibuten (45%) and mecillinam (32%). ESBL and ampC genes were present in 47 (30%) and 59 (38%) isolates.</p><p><b>CONCLUSION</b>This study demonstrated few oral therapeutic options for MDR-uropathogens, with fosfomycin demonstrating the best in vitro activity.</p>

Anaerobic bacteraemia revisited: species and susceptibilities

<p><b>INTRODUCTION</b>This retrospective study was performed to evaluate the frequency of anaerobic bacteraemia over a 10-year period, and to provide updated antibiotic susceptibilities for the more clinically relevant anaerobes causing blood stream infection.</p><p><b>MATERIALS AND METHODS</b>Data were retrieved from the laboratory information system for the period 2003 to 2012. During this time, blood cultures were inoculated in Bactec™ Plus vials (BD, USA) and continuously monitored in the Bactec™ 9000 blood culture system (BD, USA). Anaerobic organisms were identified using commercial identification kits, predominantly API 20 A (bioMérieux, France) supplemented with Vitek ANC cards (bioMérieux, France) and AN-Ident discs (Oxoid, United Kingdom). A representative subset of isolates were retrieved from 2009 to 2011 and antimicrobial susceptibilities to penicillin, amoxicillin-clavulanate, clindamycin, imipenem, moxifloxacin, piperacillin-tazobactam and metronidazole were determined using the Etest method.</p><p><b>RESULTS</b>Anaerobes comprised 4.1% of all positive blood culture with 727 obligate anaerobes recovered over the 10-year period, representing a positivity rate of 0.35%. The only significant change in anaerobe positivity rates occurred between 2003 and 2004, with an increase of 0.2%. The Bacteroides fragilis group (45%) were the predominant anaerobic pathogens, followed by Clostridium species (12%), Propioniobacterium species (11%) and Fusobacterium species (6%). The most active in vitro antibiotics were imipenem, piperacillin-tazobactam, amoxicillin-clavulanate and metronidazole, with susceptibilities of 95.0%, 93.3%, 90.8% and 90.8% respectively. Resistance was high to penicillin, clindamycin and moxifl oxacin. However, there were apparent differences for antibiotic susceptibilities between species.</p><p><b>CONCLUSION</b>This study indicates that the anaerobes comprise a small but constant proportion of bloodstream isolates. Antibiotic resistance was high to some antibiotics, but metronidazole, the beta-lactam/beta-lactamase inhibitors and carbapenems retained good in vitro activity.</p>

Vancomycin-resistant Enterococci in Singaporean hospitals: 5-year results of a multi-centre surveillance programme

<p><b>INTRODUCTION</b>Vancomycin-resistant enterococci (VRE) have emerged as one of the major nosocomial antimicrobial-resistant pathogens globally. In this article, we describe the epidemiology of VRE in Singaporean public hospitals in the 5 years following the major local VRE outbreak in 2005.</p><p><b>MATERIALS AND METHODS</b>A passive laboratory surveillance programme identified non-duplicate VRE isolates from 7 hospitals from 2006 to 2010. Descriptive statistics and time-series analysis was performed on all clinical VRE isolates for each individual hospital as well as for the combined dataset.</p><p><b>RESULTS</b>There were a total of 418 VRE isolates over 5 years, of which 102 isolates (24.4%) were from clinical cultures. Between 0.4% and 0.7% of all clinical enterococcal isolates were resistant to vancomycin. The overall incidence-density of VRE did not change over time in Singapore despite 2 separate outbreaks in tertiary hospitals in 2009 and 2010. Incidence-density of clinical VRE cases fell in 2 secondary hospitals, while another 2 hospitals experienced no significant VRE infections after 2008.</p><p><b>CONCLUSION</b>The prevalence of VRE clinical isolates remains low in Singaporean public sector hospitals. However, the presence of at least 2 outbreaks in separate hospitals over the past 5 years indicates the need for continued vigilance in order to prevent any further increase in VRE prevalence locally.</p>

Antibiotic resistance in gram-negative bacilli: a Singapore perspective

<p><b>INTRODUCTION</b>Antibiotic resistance in gram-negative bacilli is an area of increasing importance. This prospective study was performed to survey antibiotic resistance in Escherichia coli (E. coli), Klebsiella spp., Pseudomonas aeruginosa and Acinetobacter spp. over a 1-year period.</p><p><b>MATERIALS AND METHODS</b>Non-duplicate isolates of E. coli, Klebsiella spp., P. aeruginosa and Acinetobacter spp. were collected from participating Singapore hospitals during defined collection periods in 2006 and 2007. Confirmatory identification and antibiotic susceptibility testing were performed at Changi General Hospital. Minimum inhibitory concentrations (MIC) to a defined panel of antibiotics were determined using microbroth dilution methods. The presence of extended-spectrum beta lactamases and AmpC beta-lactamases in Enterobacteriaceae was determined by phenotypic methods, and susceptibility results were defined using current breakpoints from the Clinical Laboratory Standards Institute (CLSI).</p><p><b>RESULTS</b>Seven hundred and forty-six gram-negative bacilli were received for testing. Resistance to extended-spectrum cephalosporins was present in a third of Enterobacteriaceae isolates, and extended-spectrum beta-lactamases (ESBL) carriage was present in 19.6% and 30.1% of E. coli and Klebsiella pneumoniae, respectively. AmpC enzymes were also detected in 8.5% and 5.6% of E. coli and K. pneumoniae isolates respectively. All Enterobacteriaceae were susceptible to imipenem and meropenem. The most active antibiotics against P. aeruginosa were amikacin, meropenem and piperacillin-tazobactam. A third of P. aeruginosa showed reduced susceptibility to polymyxin B. Carbapenem resistance was significantly higher in Acinetobacter baumannii (70.5%) than in other Acinetobacter species (25.0%). The most active antibiotic against A. baumannii was polymyxin B.</p><p><b>CONCLUSION</b>Antibiotic resistance is prevalent in gram-negative bacilli isolated from Singapore hospitals. The MIC testing surveillance programme complemented susceptibility data from wider laboratory-based surveillance, and has revealed emerging mechanisms of antibiotic resistance.</p>

A retrospective analysis of antifungal susceptibilities of Candida bloodstream isolates from Singapore hospitals

<p><b>INTRODUCTION</b>Worldwide, Candida albicans is the most common Candida species implicated in bloodstream infections. However, the proportion of non-albicans bloodstream infections is increasing. Fluconazole resistance is known to be more common in non-albicans species, but is also reported in C. albicans. This retrospective study was performed to determine the species epidemiology of Candida bloodstream infections in Singapore hospitals, and to perform susceptibility testing to a range of antifungal drugs.</p><p><b>MATERIALS AND METHODS</b>Candida spp. isolated from bloodstream infections from October 2004 to December 2006 were collected from 3 participating hospitals: a tertiary referral hospital (Singapore General Hospital), a secondary referral hospital (Changi General Hospital) and an obstetrics/paediatric hospital [KK Women's and Children's Hospital (KKWCH)]. Isolate collection was also retrospectively extended to January 2000 for KKWCH because of the limited number of cases from this hospital. Isolates were identified by a common protocol, and antifungal susceptibility testing was performed by microbroth dilution (Sensititre One, Trek Diagnostics, United Kingdom).</p><p><b>RESULTS</b>The most common isolates were C. albicans (37%), C. tropicalis (27%) and C. glabrata (16%). There were differences in species distribution between institutions, with C. parapsilosis and C. albicans predominant in KKWCH, and C. albicans and C. tropicalis predominant in the other 2 institutions. Fluconazole resistance was detected in 3.2% of all Candida spp., and 85.3% were classified as susceptible. All C. albicans and C. parapsilosis were susceptible to fluconazole and voriconazole, while susceptibility to fluconazole was much more variable for C. glabrata and C. krusei.</p><p><b>CONCLUSION</b>This study shows that C. albicans remains the predominant Candida species isolated from bloodstream infections in the 3 participating hospitals. However, non-albicans species accounted for nearly two-thirds of all cases of candidaemia. Resistance to fluconazole was uncommon, and was generally confined to C. krusei and C. glabrata.</p>

Anaerobic culture of diabetic foot infections: organisms and antimicrobial susceptibilities

<p><b>INTRODUCTION</b>The prevalence of diabetes mellitus is high in Singapore. Infections of the lower limb are significant causes of morbidity in this population. Although the aerobic bacteriology of these infections is well-documented, there is less data available on the anaerobic pathogens involved. This study sets out to describe the anaerobic bacteria associated with diabetic foot infections, and evaluates the susceptibility to 3 antimicrobials with anaerobic activity.</p><p><b>MATERIALS AND METHODS</b>Anaerobic culture was performed on operative samples taken from diabetic foot infections. Organisms were identified through standard microbiological methods and commercial identification kits. Antimicrobial susceptibility testing to clindamycin, metronidazole and imipenem was performed by agar dilution.</p><p><b>RESULTS</b>One hundred and two strains of strict anaerobic bacteria were isolated from 30 unique specimens. The predominant anaerobic isolates were Peptostreptococcus spp. (46%) and Bacteroides fragilis group (19%). Antibiotic resistance was detected for clindamycin (18%), metronidazole (1%) and imipenem (2%).</p><p><b>CONCLUSION</b>Multiple anaerobic species can be isolated from diabetic foot infections. A significant proportion of isolates are resistant to clindamycin, while resistance to imipenem and metronidazole remains low.</p>

Susceptibility of multi-resistant Gram-negative bacilli in Singapore to tigecycline as tested by agar dilution

<p><b>INTRODUCTION</b>Tigecycline is an antibiotic belonging to the glycylcycline class with in vitro activity against most Gram-negative bacteria, other than Pseudomonas aeruginosa. This study investigated the in vitro activity of tigecycline against multi-resistant isolates of Enterobacteriaceae and Acinetobacter spp. isolated from clinical specimens in Singapore.</p><p><b>MATERIALS AND METHODS</b>Minimum inhibitory concentrations (MICs) to tigecycline were determined for 173 isolates of multi-resistant Escherichia coli, Klebsiella spp., Enterobacter spp. and Acinetobacter spp. using agar dilution.</p><p><b>RESULTS</b>The MIC required to inhibit the growth of 90% of organisms varied from 0.5 to 4 mg/L for the study isolates. Based on a resistance breakpoint of >or=8 mg/L, resistance rates varied from 0% to 9%.</p><p><b>CONCLUSIONS</b>Tigecycline demonstrates good in vitro activity against multi-resistant strains of Enterobacteriaceae, with more variable activity against multi-resistant strains of Acinetobacter spp.</p>