Antibiotic utilisation and resistance over the first decade of nationally funded antimicrobial stewardship programmes in Singapore acute-care hospitals.

OBJECTIVE: The aim of this study was to describe the time series of broad-spectrum antibiotic utilisation and incidence of antibiotic-resistant organisms during the implementation of antimicrobial stewardship programmes (ASP) in Singapore. METHODS: An observational study was conducted using data from 2011 to 2020 in seven acute-care public hospitals. We applied joinpoint regressions to investigate changes in antibiotic utilisation rate and incidence density of antibiotic-resistant organisms. RESULTS: Across the seven hospitals, quarterly broad-spectrum antibiotic utilisation rate remained stable. Half-yearly incidence density of antibiotic-resistant organisms with two joinpoints at first half (H1) of 2012 and second half (H2) of 2014 decreased significantly in the second and third period with a half-yearly percentage change (HPC) of -2.9% and - 0.5%, respectively. Across the five hospitals with complete data, half-yearly broad-spectrum antibiotic utilisation rate with one joinpoint decreased significantly from H1 of 2011 to H2 of 2018 (HPC - 4.0%) and H2 of 2018 to H2 2020 (HPC - 0.5%). Incidence density of antibiotic-resistant organisms decreased significantly in the two joinpoint periods from H1 of 2012 to H2 of 2014 (HPC - 2.7%) and H2 of 2014 to H2 of 2020 (HPC - 1.0%). Ceftriaxone with one joinpoint decreased significantly from H1 of 2011 to H1 of 2014 (HPC - 6.0%) and H1 of 2014 to H2 of 2020 (HPC - 1.8%) and ceftriaxone-resistant E. coli and K. pneumoniae decreased significantly in later periods, from H2 of 2016 to H2 of 2020 (HPC - 2.5%) and H1 of 2012 to H2 of 2015 (HPC - 4.6%) respectively. Anti-pseudomonal antibiotics with one joinpoint decreased significantly from H1 of 2011 to H2 of 2014 (HPC - 4.5%) and H2 of 2014 to H2 of 2020 (HPC - 0.8%) and that of quinolones with one joinpoint at H1 of 2015 decreased significantly in the first period. C. difficile with one joinpoint increased significantly from H1 of 2011 to H1 of 2015 (HPC 3.9%) and decreased significantly from H1 of 2015 to H2 of 2020 (HPC - 4.9%). CONCLUSIONS: In the five hospitals with complete data, decrease in broad-spectrum antibiotic utilisation rate was followed by decrease in incidence density of antibiotic-resistant organisms. ASP should continue to be nationally funded as a key measure to combat antimicrobial resistance in acute care hospitals.

Antibiotic stewardship program (ASP) in palliative care: antibiotics, to give or not to give.

Antimicrobial therapy in terminally ill patients remains controversial as goals of care tend to be focused on optimizing comfort. International guidelines recommend for antibiotic stewardship program (ASP) involvement in antibiotic decisions in palliative patients. The primary objective was to evaluate the clinical impact of ASP interventions made to stop broad-spectrum intravenous antibiotics in terminally ill patients. This was a retrospective chart review of 459 terminally ill patients in Singapore General Hospital audited by ASP between December 2010 and December 2018. Antibiotic duration, time-to-terminal discharge for end-of-life care, time-to-mortality, and mortality rates of patients with antibiotics ceased or continued upon ASP recommendations were compared. A total of 283 and 176 antibiotic courses were ceased and continued post-intervention, respectively. The intervention acceptance rate was 61.7%. The 7-day mortality rate (47.3% vs 61.9%, p = 0.003) was lower in the ceased group, while 30-day mortality rate (76.0% vs 81.2%, p = 0.203) and time-to-mortality post-intervention (3 [0-24] vs 2 [0-27] days, p = 0.066) did not differ between the ceased and continued groups. After excluding the 57 patients who had antibiotics continued until death within 48 h of intervention, only time-to-mortality post-intervention was statistically significantly shorter in the ceased group (3 [0-24] vs 4 [0-27], p < 0.001). Of the 131 terminally discharged patients, antibiotic duration (4 [0-17] vs 6.5 [1-14] days, p = 0.001) and time-to-terminal discharge post-intervention (6 [0-74] vs 10.5 [3-63] days, p = 0.001) were shorter in the ceased group. Antibiotic cessation in terminally ill patients was safe, and was associated with a significantly shorter time-to-terminal discharge.

Reducing prophylactic antibiotics use in laparoscopic cholecystectomy and liver resections.

Laparoscopic cholecystectomy and liver resections are commonly performed surgical procedures which require no or less (cefazolin only) antimicrobial prophylaxis respectively in light of recent evidence. To assess the validity of this data in the local context and increase compliance to such regimens, a multi-modal intervention including, changes to hospital antibiotic prophylaxis guidelines, departmental emphasis, information technology aids (involving the creation of order templates within our electronic medical system) and physical aids (in the form of cards given to junior staff) was implemented. Results comparing a 6-month preintervention period (January 2018 to June 2018) showed no significant increase in 30-day hospital readmission rates (P = 0.8, 0.7) despite a significant rise in compliance (P = 0.04, 0.03) in laparoscopic cholecystectomy (n = 371) and liver resections respectively (n = 193) compared to the 6-month intervention period (July 2018 to December 2018). Additionally, prescription behavior for liver resections was more varied than that of laparoscopic cholecystectomy likely due to the different anatomical considerations in the prior. In conclusion, removal of antibiotic prophylaxis in laparoscopic cholecystectomy and use of cefazolin only in liver resection is not associated with any significant increase in 30-day hospital readmission rates.

The impact of healthcare worker influenza vaccination on nosocomial influenza in a tertiary hospital: an ecological study.

BACKGROUND: To protect hospitalized patients, who are more susceptible to complications of influenza, seasonal influenza vaccination of healthcare workers (HCW) has been recommended internationally. However, its effectiveness is still being debated. To assess the effectiveness of HCW influenza vaccination, we performed an ecological study to evaluate the association between healthcare worker influenza vaccination and the incidence of nosocomial influenza in a tertiary hospital within Singapore between 2013 and 2018. METHODS: Nosocomial influenza was defined as influenza among inpatients diagnosed 7 days or more after admission by laboratory testing, while healthcare worker influenza vaccination rate was defined as the proportion of healthcare workers that was vaccinated at the end of each annual seasonal vaccination exercise. A modified Poisson regression was performed to assess the association between the HCW vaccination rates and monthly nosocomial influenza incidence rates. RESULTS: Nosocomial influenza incidence rates followed the trend of non-nosocomial influenza, showing a predominant mid-year peak. Across 2,480,010 patient-days, there were 256 nosocomial influenza cases (1.03 per 10,000 patient-days). Controlling for background influenza activity and the number of influenza tests performed, no statistically significant association was observed between vaccination coverage and nosocomial influenza incidence rate although a protective effect was suggested (IRR 0.89, 95%CI:0.69-1.15, p = 0.37). CONCLUSION: No significant association was observed between influenza vaccination rates and nosocomial influenza incidence rates, although a protective effect was suggested. Aligning local HCW vaccine timing and formulation to that of the Southern Hemisphere may improve effectiveness. HCW vaccination remains important but demonstrating its effectiveness in preventing nosocomial influenza is challenging.

Clinical Experience with High-Dose Polymyxin B against Carbapenem-Resistant Gram-Negative Bacterial Infections-A Cohort Study.

Population pharmacokinetic studies have suggested that high polymyxin B (PMB) doses (≥30,000 IU/kg/day) can improve bacterial kill in carbapenem-resistant Gram-negative bacteria (CR-GNB). We aim to describe the efficacy and nephrotoxicity of patients with CR-GNB infections prescribed high-dose PMB. A single-centre cohort study was conducted from 2013 to 2016 on septic patients with CR-GNB infection and prescribed high-dose PMB (~30,000 IU/kg/day) for ≥72 h. Study outcomes included 30-day mortality and acute kidney injury (AKI) development. Factors associated with AKI were identified using multivariable regression. Forty-three patients with 58 CR-GNB received high-dose PMB; 57/58 (98.3%) CR-GNB were susceptible to PMB. The median daily dose and duration of high-dose PMB were 32,051 IU/kg/day (IQR, 29,340-34,884 IU/kg/day) and 14 days (IQR, 7-28 days), respectively. Thirty-day mortality was observed in 7 (16.3%) patients. AKI was observed in 25 (58.1%) patients with a median onset of 8 days (IQR, 6-13 days). Higher daily PMB dose (aOR,1.01; 95% CI, 1.00-1.02) and higher number of concurrent nephrotoxins (aOR, 2.14; 95% CI; 1.03-4.45) were independently associated with AKI. We observed that a sizable proportion developed AKI in CR-GNB patients described high-dose PMB; hence, the potential benefits must be weighed against increased AKI risk. Concurrent nephrotoxins should be avoided to reduce nephrotoxicity.

Who listens and who doesn't? Factors associated with adherence to antibiotic stewardship intervention in a Singaporean tertiary hospital.

INTRODUCTION: Antibiotic stewardship programmes (ASPs) can improve patient outcomes by prospective audit and feedback with interventions. However, adherence to ASP interventions is not mandatory. Identifying factors associated with improved adherence may help to enhance ASP recommendations and activities. METHODS: A retrospective cohort study was conducted, comprising all ASP interventions performed as part of the prospective audit and feedback strategy in our institution (an acute tertiary-care hospital in Singapore) from January 2016 to July 2018. Adherence to ASP intervention was ascertained based on documented compliance with the recommended interventions within 48h. Factors associated with adherence to ASP interventions, such as patient demographics, clinical condition, type of infection, and characteristics of ASP interventions were identified using the χ2 test for categorical variables. On multivariate analysis, factors independently associated with adherence to ASP intervention were identified using logistic regression. RESULTS: Adherence to ASP intervention was 81.9% (5758/7028). On univariate and multivariate analysis, interventions coupled with direct communication via phone call (adjusted odds ratio [aOR] 1.61, 95% CI 1.23-2.08) were associated with higher odds of adherence, whereas admission to a surgical unit, intervention involving carbapenem use, and recommendation to de-escalate or discontinue antibiotics were associated with lower odds of adherence to ASP interventions. CONCLUSION: Although adherence rates to ASP interventions were relatively high, interventions made to the surgical unit and recommendations related to carbapenem use were not so well received. Interventions communicated verbally via phone call were well received, highlighting the need for a close working relationship between ASP teams and hospital physicians.

A retrospective review of tuberculosis exposure among health care workers in a tertiary hospital.

BACKGROUND: We evaluated tuberculosis (TB) acquisition rate and risk factors among health care workers (HCWs) exposed to index TB patients. METHODS: We performed a retrospective cohort study on exposed HCWs from August 2016 to January 2018 at a tertiary hospital in Singapore. Demographic factors and TB exposure episodes per HCW were obtained. A modified Poisson regression model was used to identify factors associated with TB infection. RESULTS: A total of 32 TB exposure events occurred during the study period. A total of 881 HCWs with 1,536 exposure episodes were screened with QuantiFERON-TB Gold In-tube assay (QFT-GIT) at baseline and 8 weeks. A total of 129 (14.6%) HCWs had positive QFT-TB at baseline, whereas 22 (2.5%) HCWs had QFT-GIT conversion, with a latent TB infection (LTBI) rate of 1.14 cases per 100 exposure episodes per year. Foreign nationality, non-Chinese ethnicity, and age above 40 years were independently associated with baseline LTBI, whereas having >2 TB exposure episodes and working in internal medicine, medical subspecialties, and psychiatry wards were associated with QFT-GIT conversion. DISCUSSION: The QFT-GIT conversion rate among screened HCWs is low. Foreign HCWs with LTBI likely came from countries with higher TB transmission. Targeted prevention of repeated TB exposures can reduce QFT-GIT conversion. CONCLUSIONS: The study results will guide TB contact tracing protocols in health care institutions.

Timeliness of Infectious Diseases Referral and Inappropriate Antibiotic Usage Post-Referral in an Asian Tertiary Hospital.

Infectious diseases (ID) specialists advise on complicated infections and are advocates for the interventions of antibiotic stewardship programs (ASP). Early referral to ID specialists has been shown to improve patient outcomes; however, not all referrals to ID specialists are made in a timely fashion. A retrospective cross-sectional study of all referrals to ID specialists in a Singaporean tertiary hospital was conducted from January 2016 to January 2018. The following quality indicators were examined: early referral to ID specialists (within 48 h of admission) and ASP intervention for inappropriate antibiotic usage, even after referral to ID specialists. Chi-square was used for univariate analysis and logistic regression for multivariate analysis. A total of 6490 referrals over the 2-year period were analysed; of those, 36.7% (2384/6490) were from surgical disciplines, 47.0% (3050/6490) were from medical disciplines, 14.2% (922/6490) from haematology/oncology and 2.1% (134/6490) were made to the transplant ID service. Haematology/oncology patients and older patients (aged ≥ 60 years) had lower odds of early referral to ID specialists but higher odds of subsequent ASP intervention for inappropriate antibiotic usage, despite prior referral to an ID specialist. Elderly patients and haematology/oncology patients can be referred to ID specialists earlier and their antimicrobial regimens further optimised, perhaps by fostering closer cooperation between ID specialists and primary physicians.

The use of intravesical cidofovir for the treatment of adenovirus-associated haemorrhagic cystitis in a kidney transplant recipient.

Adenovirus is an important cause of haemorrhagic cystitis in kidney transplant recipients. The optimal treatment for adenovirus-associated haemorrhagic cystitis (AAHC) is unknown. Intravenous cidofovir may be effective, but nephrotoxicity is a major concern. The use of intravesical cidofovir for viral haemorrhagic cystitis has been reported in haematopoietic stem cell transplant recipients and may be associated with a lower risk of nephrotoxicity, but its use has not been reported in kidney transplant recipients. We report the use of intravesical cidofovir for the treatment of AAHC in a kidney transplant recipients, along with a review of the literature.

Do antimicrobial stewardship programme interventions reduce the rate of and protect against Clostridium difficile infection?

OBJECTIVES: Antimicrobial stewardship programmes (ASPs) have often been recommended as a viable solution to minimise the incidence of Clostridium difficile infection (CDI), which can be life-threatening. This study aimed to evaluate whether ASP interventions have contributed to reducing CDI rates. METHODS: A retrospective review of ASP interventions issued from January 2013 to April 2014 was performed using data from the ASP database of Singapore General Hospital, a 1600-bed tertiary-care hospital in Singapore. A total of 283 interventions satisfied the inclusion criteria, of which commonly audited antibiotics were piperacillin/tazobactam (41.3%) and carbapenems (54.8%). Comparisons were made at 30days post-intervention between those with accepted or rejected interventions. The primary outcome was CDI incidence; secondary outcomes included length of hospitalisation post-intervention, 30-day mortality and CDI recurrence rate. RESULTS: Whilst the median duration of antibiotic therapy was reduced by 2days (6days vs. 4 days; P<0.001), acceptance of ASP interventions did not alter primary CDI incidence at 30days (P=0.644) post-intervention. However, reduced CDI recurrence rates were observed for patients positive for CDI in the accepted patient group compared with the rejected group (0% vs. 37.5%; P=0.03), with no difference in CDI 30-day mortality between the two groups. CONCLUSION: Intervention acceptance did not contribute to a significant reduction in CDI incidence but may be associated with lower recurrence rates, although further studies are required.

Urinary tract infections in adults.

A urinary tract infection (UTI) is a collective term for infections that involve any part of the urinary tract. It is one of the most common infections in local primary care. The incidence of UTIs in adult males aged under 50 years is low, with adult women being 30 times more likely than men to develop a UTI. Appropriate classification of UTI into simple or complicated forms guides its management and the ORENUC classification can be used. Diagnosis of a UTI is based on a focused history, with appropriate investigations depending on individual risk factors. Simple uncomplicated cystitis responds very well to oral antibiotics, but complicated UTIs may require early imaging, and referral to the emergency department or hospitalisation to prevent urosepsis may be warranted. Escherichia coli remains the predominant uropathogen in acute community-acquired uncomplicated UTIs and amoxicillin-clavulanate is useful as a first-line antibiotic. Family physicians are capable of managing most UTIs if guided by appropriate history, investigations and appropriate antibiotics to achieve good outcomes and minimise antibiotic resistance.

Candida Surveillance in Surgical Intensive Care Unit (SICU) in a Tertiary Institution.

BACKGROUND: Colonization of patients occurs before development into invasive candidiasis. There is a need to determine the incidences of Candida colonization and infection in SICU patients, and evaluate the usefulness of beta-D-glucan (BDG) assay in diagnosing invasive candidiasis when patients are colonized. METHODS: Clinical data and fungal surveillance cultures in 28 patients were recorded from November 2010, and January to February 2011. Susceptibilities of Candida isolates to fluconazole, voriconazole, amphotericin B, micafungin, caspofungin and anidulafungin were tested via Etest. The utilities of BDG, Candida score and colonization index for candidiasis diagnosis were compared via ROC. RESULTS: 30 BDG assays were performed in 28 patients. Four assay cases had concurrent colonization and infection; 23 had concurrent colonization and no infection; three had no concurrent colonization and infection. Of 136 surveillance swabs, 52 (38.24 %) were positive for Candida spp, with C. albicans being the commonest. Azole resistance was detected in C. albicans (7 %). C. glabrata and C. tropicalis were, respectively, 100 and 7 % SDD to fluconazole. All 3 tests showed high sensitivity of 75-100 % but poor specificity ranging 15.38-38.46 %. BDG performed the best (AUC of 0.89). CONCLUSIONS: Despite that positive BDG is common in surgical patients with Candida spp colonization, BDG performed the best when compared to CI and CS.

Role of antibiotic prophylaxis in necrotizing pancreatitis: a meta-analysis.

UNLABELLED: Several studies have yielded conflicting results on the role of antibiotic prophylaxis in improving outcomes in acute necrotizing pancreatitis. A meta-analysis was carried out to investigate the impact of antibiotic prophylaxis in the incidence of infected pancreatic necrosis and mortality. METHODOLOGY: Randomized controlled trials and cohort studies investigating impact of prophylactic systemic antibiotic used in acute necrotizing pancreatitis were retrieved from online databases. An overall analysis was done with all studies (Group 1), followed by subgroup analyses with randomized controlled trials (Group 2) and cohort studies (Group 3). Risk ratios (RR) were calculated for the impact of antibiotic prophylaxis in the incidence of infected pancreatic necrosis and mortality in each group using random effects model. RESULTS: Eleven studies involving 864 patients were included. No significant differences in the incidence of infected pancreatic necrosis were observed with prophylactic antibiotic use in all groups. Prophylactic antibiotic use was not associated with significant differences in all-cause mortality in Group 2 (RR = 0.75; p = 0.24) but was associated with a reduction in Groups 1 (RR = 0.66, p = 0.02) and 3 (RR = 0.55, p = 0.04). There was no statistical difference in the incidence of fungal infections and surgical interventions. CONCLUSION: Antibiotic prophylaxis does not significantly reduce the incidence of infected pancreatic necrosis but may affect all-cause mortality in acute necrotizing pancreatitis.

Prospective audit and feedback in antimicrobial stewardship: is there value in early reviewing within 48 h of antibiotic prescription?

Antimicrobial stewardship programme (ASP) methodologies are not well defined, with most preferring to wait ≥72-96 h following antibiotic prescription before reviewing patients. However, we hypothesise that early ASP reviews and interventions are beneficial and do not adversely impact patient safety. This study aimed to evaluate the impact of early ASP interventions within 48 h of antibiotic prescription on patient outcomes and safety. A prospective review of ASP interventions made within 48 h of antibiotic prescription in Singapore General Hospital (SGH) from January to December 2012 was conducted. Patient demographics and outcomes were extracted from the database maintained by the ASP team. For culture-directed treatment, there was a shorter mean duration of therapy (DOT) in the accepted group compared with the rejected group (2.26 days vs. 5.56 days; P<0.001). ASP interventions did not alter the length of hospital stay (LOS), 30-day mortality, 14-day Clostridium difficile infection (CDI), 30-day re-admissions and 14-day re-infection (all P>0.05). For empirical treatment, a shorter DOT (3.61 days vs. 6.25 days; P<0.001) and decreased 30-day all-cause mortality (P=0.003) and infection-related mortality (P=0.002) were observed among patients in the accepted group compared with the rejected group. There was no significant difference in LOS, 14-day CDI and 30-day re-admission (all P>0.05). In conclusion, acceptance of early interventions recommended by ASP in SGH was associated with a reduction in DOT without compromising patient safety. This is evident even during empirical therapy when not all clinical information was available.

Nonattenuated Polymyxin B Used for the Treatment of Extreme-Drug Resistant Acinetobacter baumannii-Related Infections in Patients with Preexisting End Stage Renal Failure.

Recent pharmacokinetic studies have suggested that nonrenal clearance predominates the elimination of polymyxin B. We present 2 patients with preexisting end stage renal failure, who were given nonattenuated doses of polymyxin B for the treatment of extreme-drug resistant organism. No evidence of adverse events occurred and microbiological clearance was documented.

Recurrent cellulitis: risk factors, etiology, pathogenesis and treatment.

Erysipelas and uncomplicated cellulitis are common infections that tend to recur in a substantial proportion of affected patients following an initial episode, especially if the predisposing condition is chronic lymphedema. All patients who suffer an episode of cellulitis should be carefully evaluated to establish the risk of recurrence. Several predisposing conditions (such as lymphedema and skin conditions that serve as a portal of entry for bacteria) can be effectively treated in order to reduce the risk of relapse. The medical literature provides convincing evidence that antimicrobial prophylaxis can markedly reduce the frequency of relapse of erysipelas. Two recent studies performed by the 'Prophylactic Antibiotics for the Treatment of Cellulitis at Home' (PATCH) group have clearly confirmed the efficacy of antimicrobial prophylaxis. Penicillin remains the drug of choice. Treatment options in patients with penicillin allergy are limited by the rising prevalence of macrolide resistance among group A streptococci. Further research is required to clarify the optimal penicillin regimen as well as to develop new therapies for patients with allergy to penicillin.

An Observational Study on Early Empiric versus Culture-Directed Antifungal Therapy in Critically Ill with Intra-Abdominal Sepsis.

Objective. To compare early empiric antifungal treatment with culture-directed treatment in critically ill patients with intra-abdominal sepsis. Methods. A prospective observational cohort study was conducted between August 2010 and July 2011, on SICU patients admitted after surgery for gastrointestinal perforation, bowel obstruction or ischemia, malignancy and anastomotic leakages. Patients who received antifungal treatment within two days of sepsis onset were compared to patients who received culture-directed antifungal treatment in terms of mortality rate and clinical improvement. Patients' demographics, comorbidities, severity-of-illness scores, and laboratory results were systematically collected and analysed. Results. Thirty-three patients received early empiric and 19 received culture-directed therapy. Of these, 30 from the early empiric group and 18 from culture-directed group were evaluable and analysed. Both groups had similar baseline characteristics and illness severity. Patients on empiric antifungal use had significantly lower 30-day mortality (P = 0.03) as well as shorter median time to clinical improvement (P = 0.025). Early empiric antifungal therapy was independently associated with survival beyond 30 days (OR 0.131, 95% CI: 0.018 to 0.966; P = 0.046). Conclusion. Early empiric antifungal therapy in surgical patients with intra-abdominal sepsis was associated with reduced mortality and warrants further evaluation in randomised controlled trials.