Living with COVID-19: The road ahead

INTRODUCTION@#The COVID-19 pandemic has affected the world for more than a year, with multiple waves of infections resulting in morbidity, mortality and disruption to the economy and society. Response measures employed to control it have generally been effective but are unlikely to be sustainable over the long term.@*METHODS@#We examined the evidence for a vaccine-driven COVID-19 exit strategy including academic papers, governmental reports and epidemiological data, and discuss the shift from the current pandemic footing to an endemic approach similar to influenza and other respiratory infectious diseases.@*RESULTS@#A desired endemic state is characterised by a baseline prevalence of infections with a generally mild disease profile that can be sustainably managed by the healthcare system, together with the resumption of near normalcy in human activities. Such an endemic state is attainable for COVID-19 given the promising data around vaccine efficacy, although uncertainty remains around vaccine immunity escape in emergent variants of concern. Maintenance of non-pharmaceutical interventions remains crucial until high vaccination coverage is attained to avoid runaway outbreaks. It may also be worthwhile to de-escalate measures in phases, before standing down most measures for an endemic state. If a variant that substantially evades immunity emerges, it will need to be managed akin to a new disease threat, with pandemic preparedness and response plans.@*CONCLUSION@#An endemic state for COVID-19, characterised by sustainable disease control measures, is likely attainable through vaccination.

Infuenza and Patients with Chronic Diseases and Elderly

@#Influenza is a highly contagious viral illness characterized by fever, cough, headache and myalgia. The influenza virus is a segmented ribonucleic acid (RNA) virus that can infect both humans and animals, and the capacity for reassortment when multiple viruses infect the same cell has led – and will continue to lead – to the development of novel pandemic influenza A viruses. The disease is generally self-limiting, although complications and deaths can occur, particularly in children < two years of age, adults >65 years of age, pregnant women, and immunosuppressed individuals. Specific antiviral therapy is available, including oseltamivir in Singapore, and is recommended for severe disease as well as those with higher likelihood for developing complications from influenza. In addition to hand hygiene and respiratory etiquette, antiviral prophylaxis may reduce the impact and burden of influenza in household and institutional settings. However, the primary means for preventing influenza is via annual vaccination in those above the age of two years. The influenza vaccine, while having variable efficacy depending on antigenic matching with circulating viruses each year, is safe and cost-effective at the population level.

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.

Ministry of Health Clinical Practice Guidelines: Prevention, Diagnosis and Management of Tuberculosis

The Ministry of Health (MOH) has developed the clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis to provide doctors and patients in Singapore with evidence-based treatment for tuberculosis. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis, for the information of SMJ readers. The chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Ceftaroline--An Anti-MRSA Cephalosporin and Its Implications for Singapore

<p><b>INTRODUCTION</b>Ceftaroline is a fifth-generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) that was recently launched in Singapore. It received approval from the United States (US) Food Drug Administration (FDA) and European Commission for the treatment of adult patients with community-acquired pneumonia (CAP) and complicated skin and soft tissue infections (cSSTI). This study aimed to review current published data and determine its clinical role, particularly in the local setting.</p><p><b>MATERIALS AND METHODS</b>A literature review on published articles in English on ceftaroline, focusing in particular on clinical trials and other clinical reports. Susceptibility testing was also performed on a limited sample of local MRSA and Streptococcus pneumoniae isolates.</p><p><b>RESULTS</b>Ceftaroline has an extensive spectrum of activity, including coverage of MRSA and multidrug-resistant S. pneumoniae. However, it has limited activity against non-fermenting Gram-negative bacteria and is susceptible to hydrolysis by extended spectrum beta-lactamases. It is only available for intravenous delivery, with a reconstituted stability of just 6 hours, rendering it unavailable for use for outpatient antibiotic therapy. Clinical trials demonstrate non-inferiority compared to first-line comparators in the treatment of CAP and cSSTI. Published case reports/series suggest a potential greater role in the treatment of MRSA bacteremia and endocarditis. No resistance was found among local archived MRSA and S. pneumoniae isolates.</p><p><b>CONCLUSION</b>We believe ceftaroline will occupy primarily niche roles for culture-directed treatment of various infections--in particular those caused by MRSA--until further clinical trial data become available. A variety of factors render it less useful or appealing for empirical treatment of CAP or healthcare-associated infections.</p>

An Outbreak of Community Associated Methicillin Resistant Staphylococcus aureus Subtype USA300 at an International School in Singapore

Community associated methicillin-resistant Staphylococcus aureus (CA-MRSA) subtype USA300 remains relatively well confined within North American shores. Between August and November 2010, a large international school in Singapore recorded 27 skin and soft tissue infections, 8 of which were confirmed USA 300. This study reports the outbreak investigation and the interventions instituted.

The excess financial burden of multidrug resistance in severe gram-negative infections in Singaporean hospitals

<p><b>INTRODUCTION</b>Multidrug-resistant (MDR) Gram-negative healthcare-associated infections are prevalent in Singaporean hospitals. An accurate assessment of the socioeconomic impact of these infections is necessary in order to facilitate appropriate resource allocation, and to judge the costeffectiveness of targeted interventions.</p><p><b>MATERIALS AND METHODS</b>A retrospective cohort study involving inpatients with healthcare-associated Gram-negative bacteraemia at 2 large Singaporean hospitals was conducted to determine the hospitalisation costs attributed to multidrug resistance, and to elucidate factors affecting the financial impact of these infections. Data were obtained from hospital administrative, clinical and financial records, and analysed using a multivariate linear regression model.</p><p><b>RESULTS</b>There were 525 survivors of healthcare-associated Gram-negative bacteraemia in the study cohort, with 224 MDR cases. MDR bacteraemia, concomitant skin and soft tissue infection, higher APACHE II score, ICU stay, and appropriate definitive antibiotic therapy were independently associated with higher total hospitalisation costs, whereas higher Charlson comorbidity index and concomitant urinary tract infection were associated with lower costs. The excess hospitalisation costs attributed to MDR infection was $8638.58. In the study cohort, on average, 62.3% of the excess cost attributed to MDR infection was paid for by government subvention.</p><p><b>CONCLUSION</b>Multidrug resistance in healthcare-associated Gram-negative bacteraemia is associated with higher financial costs--a significant proportion of which are subsidised by public funding in the form of governmental subvention. More active interventions aimed at controlling antimicrobial resistance are warranted, and the results of our study also provide possible benchmarks against which the cost-effectiveness of such interventions can be assessed.</p>

Prospective audit of post-chemotherapy febrile neutropenia in patients with solid cancer and lymphoma in two Singaporean cancer centres

<p><b>INTRODUCTION</b>Febrile neutropenia (FN) is a significant cause of mortality and morbidity in oncology and haematology units worldwide. The overall mortality in hospital surveys in Singapore surveys on post-chemotherapy FN has ranged between 3.0% and 8.8%. However, recent evidence indicates that outpatient management of patients with low-risk FN is safe and cost-effective.</p><p><b>MATERIALS AND METHODS</b>We conducted a prospective audit on a cohort of adult patients with post-chemotherapy FN seen at 2 local public sector cancer centres over a 1-year period in order to define their epidemiological characteristics and outcomes, and also to assess the uptake of early discharge/outpatient management strategies for these patients.</p><p><b>RESULTS</b>We reviewed 306 FN episodes from 248 patients. Patient characteristics and outcomes were similar between both institutions. Eleven (3.7%) FN episodes were managed as outpatient and none developed complications. Overall 30-day mortality was 6.6%, while the median length of stay (LOS) was 7 days (IQR: 4 to 11 days). The only independent risk factor for mortality was severe sepsis (OR:13.19; 95% CI: 1.98 to 87.7; P = 0.008). Factors independently associated with a longer LOS were vancomycin prescription (coefficient: 0.25; 95% CI: 0.08 to 0.41; P = 0.003), longer duration of intravenous antibiotics (coefficient: 0.08; 95% CI: 0.06 to 0.10; P <0.001), and prior review by an infectious diseases physician (coefficient: 0.16; 95% CI: 0.01 to 0.31; P = 0.034).</p><p><b>CONCLUSION</b>This audit demonstrated that mortality from FN in our 2 cancer centres is low and comparable to international institutions. It also demonstrates that outpatient management of FN is safe in selected patients, and can be further expanded for right-siting of resources.</p>

Risk factors for adverse outcomes and multidrug-resistant Gram-negative bacteraemia in haematology patients with febrile neutropenia in a Singaporean university hospital

<p><b>INTRODUCTION</b>Institutional febrile neutropenia (FN) management protocols were changed following the finding of a high prevalence of ceftazidime-resistant Gram-negative bacteraemia (CR-GNB) among haematology patients with FN. Piperacillin/tazobactam replaced ceftazidime as the initial empirical antibiotic of choice, whereas carbapenems were prescribed empirically for patients with recent extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae colonisation/infection. An audit was conducted to determine the impact of these changes.</p><p><b>METHODS</b>Data from all FN episodes between October 2008 and December 2010 were collected prospectively, with mid-November 2009 demarking the transition between pre-intervention and intervention periods. Outcomes measured included 30-day mortality post-development of FN and the presence of CR-GNB.</p><p><b>RESULTS</b>There were 427 FN episodes (200 in the pre-intervention period) from 225 patients. The prevalence of CRGNB was 10.3%, while the 30-day mortality was 4.7%, with no difference between pre-intervention and intervention periods. Independent risk factors for 30-day mortality included the presence of active haematological disease, vancomycin prescription and older age. Independent factors associated with initial CR-GNB were profound neutropenia, the presence of severe sepsis and active haematological disease. Recent ESBL-producing Enterobacteriaceae colonisation/infection was not predictive of subsequent CR-GNB (positive predictive value 17.3%), whereas a model based on independent risk factors had better negative predictive value (95.4%) but similarly poor positive predictive value (21.4%), despite higher sensitivity.</p><p><b>CONCLUSION</b>A change in the FN protocol did not result in improved outcomes. Nonetheless, the audit highlighted that empirical carbapenem prescription may be unnecessary in FN episodes without evidence of severe sepsis or septic shock, regardless of previous microbiology results.</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>

Prospective audit of febrile neutropenia management at a tertiary university hospital in Singapore

<p><b>INTRODUCTION</b>Febrile neutropenia (FN) remains a major cause of morbidity and mortality in Oncology/Haematology units. We launched a new protocol for FN management that incorporates risk stratification at our institute from October 2008. An audit was performed concurrently to evaluate the protocol and to define the epidemiology of FN locally.</p><p><b>MATERIALS AND METHODS</b>Case records of all inpatients with FN between October 2008 and June 2009 were reviewed prospectively. Clinical and microbiological characteristics were collated along with outcomes and programme adherence. Statistical testing was performed using Stata 10.1.</p><p><b>RESULTS</b>There were 178 FN episodes (50 in patients with solid cancers) from 131 patients. Forty-two (23.6%) episodes were classified as high-risk according to MASCC criteria. Initial blood cultures were positive in 49 (27.5%) episodes, of which gram-negative bacilli (GNB) predominated. Overall compliance to the protocol was 56.7%, with the main issue being disinclination to use oral antibiotics as fi rst-line empirical therapy for low-risk episodes. Overall mortality was 7.3% and infection-related mortality was 4.5%. High-risk FN and the presence of central venous catheters were independently associated with bacteraemia on multivariate analysis, but there were no independent predictors of infection-related mortality.</p><p><b>CONCLUSIONS</b>GNB accounted for the majority of bloodstream infections at our institute, unlike data from developed countries. Uptake of the new FN protocol was satisfactory, although the use of oral antibiotics as fi rst-line empirical therapy can be improved. A better method for predicting infections caused by antibiotic-resistant GNB is urgently required, and antibiotic resistance trends should be monitored to enable the implementation of more appropriate antibiotic regimens over time.</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>

Cluster of Staphylococcus aureus and dengue co-infection in Singapore

<p><b>INTRODUCTION</b>Singapore saw a resurgence of dengue infections in 2005. Concurrent bacterial co-infections in dengue is rare.</p><p><b>CLINICAL PICTURE</b>We report a cluster of serious methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia or severe soft tissue infection in 5 epidemiologically linked construction workers presenting with dengue and non-resolving fever.</p><p><b>TREATMENT</b>Surgical intervention was indicated in 4 of the 5 patients despite appropriate antistaphylococcal therapy.</p><p><b>OUTCOME</b>All but 1 patient were eventually discharged. Clonality and Panton-Valentine leucocidin genes were not demonstrated. Epidemiological investigations suggested that occupational contact dermatitis could have predisposed the patients to this opportunistic co-infection.</p><p><b>CONCLUSION</b>Clinicians need to be vigilant to unusual manifestations of dengue which may signal a concomitant aetiology.</p>

Tetanus in an injecting buprenorphine abuser

<p><b>INTRODUCTION</b>Injecting drug abusers are vulnerable to many infectious complications. We describe a case of tetanus in a Singaporean who regularly abused buprenorphine.</p><p><b>CLINICAL PICTURE</b>A 49-year-old male was hospitalised for progressive generalised spasms associated with dysarthria and opisthotonus. Tetanus was diagnosed clinically.</p><p><b>TREATMENT</b>Supportive management was instituted in the intensive care unit (ICU). Toxicology samples tested positive for buprenorphine.</p><p><b>OUTCOME</b>He recovered rapidly and was transferred out of the ICU after 8 days. Retrospective questioning confirmed parenteral abuse of buprenorphine.</p><p><b>CONCLUSION</b>This case highlights an uncommon and potentially lethal complication of parenteral drug abuse.</p>

Community-associated methicillin-resistant Staphylococcus aureus: overview and local situation

<p><b>INTRODUCTION</b>Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged worldwide. In contrast to healthcare-associated MRSA (HA-MRSA), CA-MRSA isolates are usually susceptible to multiple non-beta-lactam antibiotics and cause a distinct spectrum of infections in epidemiologically disparate populations - in particular, cutaneous abscesses, necrotising fasciitis and necrotising pneumonia. They arise from a broader genetic background, and possess differing virulence genes. We aim to describe the distribution of different molecular subtypes of CA-MRSA among various regions and discuss briefly the implications of CA-MRSA from a local perspective.</p><p><b>METHODS</b>Literature review of articles on CA-MRSA, focusing mainly on reports where the genetic background of isolates had been analysed using multi-locus sequence typing (MLST). Singapore data were obtained from the local CA-MRSA database.</p><p><b>RESULTS</b>MLST analysis demonstrated the presence of epidemic subtypes of CA-MRSA within most geographic areas. In parts of the United States, community MRSA infections currently exceed those caused by their methicillin-susceptible counterparts. In Singapore, CA-MRSA infections are increasing, predominantly as a result of the spread of ST30 clones.</p><p><b>CONCLUSION</b>Available evidence suggests that the emergence of MRSA from the community is not going to be a transient phenomenon. Local guidelines for dealing with this phenomenon at both therapeutic and preventive levels are needed prior to the potential development of a situation mirroring that of meso-endemic HA-MRSA in local hospitals or CA-MRSA epidemics in parts of USA.</p>